Selected methods of extracting carotenoids, characterization and

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Selected methods of extracting carotenoids, characterization and health concern: a Review Parise Adadi, Barakova Nadezhda Vasilyevna, and Elena Fedorovna Krivoshapkina J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.8b01407 • Publication Date (Web): 31 May 2018 Downloaded from http://pubs.acs.org on May 31, 2018

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Journal of Agricultural and Food Chemistry

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Selected methods of extracting carotenoids, characterization and health concern: a Review

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Parise Adadi*, Nadezhda Vasilyevna Barakova, Elena Fedorovna Krivoshapkina

5 6

ITMO University, Lomonosova Street. 9, 191002, St. Petersburg, Russia Federation

7 8 9 10 11 12 13

* Address correspondence to this author at Laboratory of Solution Chemistry of Advanced

14

Materials and Technologies (SCAMT), Department of Food Biotechnology (Vegetable

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stock), ITMO University, Lomonosova Street. 9, 191002, St. Petersburg, Telephone:

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+79817511640. e-mail: [email protected]/[email protected]; ORCID ID

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0000-0003-4724-9463

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Abstract: Carotenoids are the most powerful nutrients (medicine) on earth due to their potent

26

antioxidant properties. The ability of these tetraterpenoids in obviating human chronic

27

ailments like cancer, cardiovascular disease, osteoporosis, and diabetes has drawn public

28

attention toward these novel compounds. Conventionally, carotenoids have been extracted

29

from plant materials and agro-industrial by-product using different solvents, but these

30

procedures result in contaminating the target compound (carotenoids) with extraction

31

solvents. Furthermore, some solvents utilize are not safe hence harmful to the environment.

32

This had attracted criticism from consumers, ecologists, environmentalists and public health

33

workers. However, there is clear consumer preference for carotenoids from natural origin

34

without traces of extracting solvent. Therefore, this review seeks to discuss methods for

35

higher recovery of pure carotenoids without contamination from a solvent. Methods such as

36

Enzyme-based extraction, Supercritical fluid extraction, Microwave-assisted extraction,

37

Soxhlet extraction, Ultrasonic extraction and post-extraction treatment (saponification) are

38

discussed. Merits and demerits of these methods as while as health concerns during intake of

39

carotenoids were also considered.

40 41

Keywords: Antioxidant, Cancer, α- and β-carotenes, Functional food, Plant materials.

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1. Introduction

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According to

53

and microorganisms but not animals. They are responsible for photosynthetic mechanisms

54

and protecting plants against photo-damage. The chemical structure of carotenoids is

55

composed of a polyene skeleton which usually consists of 40 carbon atoms and is either

56

acyclic or terminated by one or two cyclic end groups 2. The colors of these pigments range

57

from yellow to red and are found in tomatoes (lycopene Fig. 1B), maize corn (zeaxanthin)

58

and carrot (β-carotene) 3. This group of valuable molecules are of interest to food and feed

59

companies, chemical and pharmaceutical firms not because they act as vitamin A precursor

60

but their antioxidant, color and anti-tumor activities 4. The potential role of carotenoids in

61

averting prostate cancer and cardiovascular diseases in humans has recently gained attention

62

globally. Owing to its antioxidant potency, it possesses the ability to act as a free radical

63

scavenger. In biological systems, lycopene has the highest singlet oxygen-quenching rate

64

than all the carotenoids 5-10. Carotenoids are used in cosmetic products (pomades) due to their

65

Photo-protection abilities against ultraviolet (UV) radiation. Keratinocytes (an epidermal cell

66

which generates keratin to serves as a barrier) present in the epidermis of skin absorbs UV-B

67

radiations (280–315 nm) and UV-A radiation (320-400 nm) which can lead to the

68

development of erythema and UV-carcinogenesis respectively 11.

69

According to

70

due to oxidation, losses and time. Much time is wasted during incubation periods, for

71

instance,

72

consuming and not practical on an industrial scale of extraction. Conventionally, carotenoids

73

have been extracted from fruits and vegetables using different solvents, but in general, these

13

1

carotenoids are class of pigmented compounds that are synthesized in plants

12

, researchers face challenges during extraction of these valuable compounds

using benzene and boiling methanol to wash crystals 10 times, which is time-

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procedures result in contaminating the extraction solvents. However, there is a clear

75

consumer preference for carotenoids without traces of extracting solvent.

76

For this reason, a lot of resources (particularly huge sums of money) has been allocated for

77

scientific research on the extraction of bioactive compounds for the development of the

78

functional foods. The most potent antioxidant amongst all carotenoids is the lycopene which

79

is widely used in healthcare products, food and cosmetics 14.

80

With a huge population of low-income earners in most African countries, a large portion of

81

the people cannot afford daily balanced diet coupled with the fact that fruits consumption

82

after a meal is not widely practiced among the people, hence exposure to diseases which

83

could be prevented by carotenoids becomes pronounced. Nutraceutical supplements of these

84

carotenoids are already in the market for purchase. For example, FloraGLO®-lutein,

85

Cathatene 10% FT (fluid type), Lycotone-XX, Alpha GPC capsules can be purchased and

86

taken as a supplement or as food additives i.e adding to beverages. For these reasons, a lot of

87

research has sprung up with the scientific interest of investigating for alternate methods of

88

extraction, different from the conventional solvent extractions. Therefore, Enzyme-based

89

extraction, Supercritical fluid extraction, Microwave-assisted extraction, Soxhlet extraction,

90

and Ultrasonic extraction is considered in this review as real options for carotenoid

91

extraction. Furthermore, the classifications, type, and biosynthesis of carotenoids are

92

discussed.

93

2. Sources of carotenoids

94

2.1. Plant

95

Dark green vegetables, colored fruits, and flowers are the main sources of natural carotenoids

96

15

97

β-carotene,

98

canthaxanthin, and capsanthin are the major carotenoids which can be extracted from fruits

. Food sources and quantity of carotenoids present are shown in Table 1. According to 18,19 α-carotene,

β-cryptoxanthin,

lycopene,

lutein,

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zeaxanthin,

neoxanthin,

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and vegetables due to the yellow-orange pigments. Carrots, cantaloupe, spinach, lettuce,

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tomatoes, sweet potatoes, and broccoli are rich sources of β-carotene. Canola and Golden rice

101

are excellent sources as well. Some fruits and vegetables can serve as sources of both α and β

102

carotenes.

103

Ripening and conditions during processing affect the content of carotenoids i.e the ratio of β-

104

carotene and β-cryptoxanthin can be altered

105

discovered the bioavailability of β-carotene would be improved drastically in the presence of

106

dietary fat.

107

β-cryptoxanthin occurs predominately in Citrus unshiu MARC

108

peach, papaya, orange, and tangerine also contain some amount 27. Persimmon (Diospyros

109

kaki), Squash/pumpkin (Cucurbita spp), Pepper (red, orange) (C. annuum) and Loquat

110

(Eriobotrya japonica) are other sources of β –cryptoxanthin 28.

111

Green leafy vegetables are the rich source of lutein and zeaxanthin. However, these yellow

112

pigments are also in produce like zucchini, spinach, broccoli, squash, kiwi fruit, grapes,

113

orange juice, yellow capsicums, persimmons, tangerines, mandarins. The highest

114

concentrations of lutein and zeaxanthin are present in maize (60% of the total carotenoids)

115

and Egg yolk

116

carotene, lycopene, zeaxanthin. Moreover, oils from seed, fruit pulp (juice), and fruit residue

117

of H. rhamnoides after removing juice is thought to also contain carotenoids in a range

118

between 30-250, 300-850 and 1280-1860 mg/g respectively 32. Sommerburg et al. 33 reported

119

that orange pepper and wolfberry was rich in zeaxanthin. Spinach, celery (stalks and leaves),

120

Brussels sprouts and scallions, broccoli, lettuce (green) were found to be good sources of

121

lutein with varying quantities of 47, 34, 27, 22, and 15% respectively. According to

122

skin pigmentation of birds, egg yolk, in pigs and some fishes (salmon) are the imparts of

123

zeaxanthin. The red hues in vegetables (tomatoes and its products i.e tomato sauce, tomato

20,21

. From previous studies by

22,23,24

, it was

25,26

, however, fruits such as

29,30,31

. Sea buckthorn (Hippophae rhamnoides) was found to contain β-

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the

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soup, and tomato juice) and fruits (watermelon, Gac) are the results of lycopene. Other

125

sources include papaya, guava, apricot, autumn olive 35, Japanese persimmon 36, pitanga ripe

126

fruit 37, red cabbage 38, carrot, red roots 39,40, and Bitter melon 41. Tomatoes contain about 3.1

127

mg per 100 g of lycopene 31. A recent paper published by 42, revealed that dehydrating plant

128

matrixes gave the higher yield of lycopene. Fresh and freeze-dried matrices of Gac, Tomato

129

and Watermelon contains 1.34 ± 0.19, 0.22 ± 0.03, 0.05 ± 0.01 and 4.5 ± 0.2, 10.6 ± 0.4 and

130

2.2 ± 0.1 (g/kg f-DW) of lycopene respectively. Nevertheless, the freeze-dried matrices

131

contain 3-, 40-, and 82-fold of total lipids than the fresh plant materials respectively.

132

Neoxanthin and violaxanthin (xanthophyll epoxy-carotenoids) are predominant in potherbs.

133

The major sources include leek (1.0 mg/100 mg), arugula (1.0 mg/100 g), and lamb’s lettuce

134

(0.9mg/100 g) and yellow bell peppers (4.4 mg/100 g), spinach (2.8 mg/100 g), creamed

135

spinach (2.5 mg/100 g) for Neoxanthin and violaxanthin, respectively 31.

136

As cited by 43 angiosperms also contain significant quota of neoxanthin and violaxanthin with

137

Canna indica making 8% of the carotenoids. Fatimah et al. 17, detected the highest amount of

138

neoxanthin (235.36 ± 11.02 µg/g DW) and violaxanthin (83.98 ± 6.86

139

mengkudu, and pegaga respectively.

140

Mushroom, Capsicum annum, and saffron plant are the main sources of canthaxanthin,

141

capsanthin, capsorubin, crocin, and crocetin

142

mushroom were also identified to contain canthaxanthin

143

carotenoids like crocin and crocetin which are mainly utilized as a colorant in the food

144

industries 46. Moreover, Capsanthin is also used as food colorant present in Sweet and chili

145

peppers 31.

146

2.2. Microbial sources

147

Microbial production of carotenoids allows for a more sustainable and environmentally-

148

friendly approach than some of the conventional chemical methods of extraction. Algae,

µg/g

DW) in

44

. Marine algae and crustaceans aside 45

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. Crocus sativus L. produces

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fungi, bacteria, marine organisms (photosynthetic organisms) and vertebrates a synthesized

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wide variety of carotenoids 44,47,48 (Table 2).

151

2.2.1. Algae and marine organism (grasses and animals)

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Specific functions and unique structure of carotenoids extracted from algae and other marine

153

organisms are of interest in the food and pharmaceutical industries. Algae are considered to

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be a rich source of other bioactive molecules which have a positive impact on human health

155

49,50

156

synthesized in some divisions whilst β-Carotene and zeaxanthin are found in all the classes of

157

algae. The strains Chlorococcales can produce carotenoids include astaxanthin, echinenone,

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ketocarotenoids, and canthaxanthin 51,52. Del Campo et al. 53 and Hagen et al. 54 reported that

159

Haematococcus pluvialis, Chlorococcum sp., Chlorella zofingiensis, and Chlorella vulgaris

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(chlorophyte) synthesized predominantly astaxanthin and its derivatives. Zeaxanthin is found

161

in both red (Porphyridium cruentum and Gracilaria Damaecornis) and brown algae

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(Macrocystis pyrifera) although their predominant in the species like Nannochloropsis

163

oculata, Chaetoceros gracilis, Dunaliella salina

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green (Chlorophyta) algal species are the major sources of lutein 52,56.

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Chlorophyta produced mainly violaxanthin and neoxanthin whereas Heterokontophyta,

166

Haptophyta, Dinophyta, and Euglenophyta are the major source of diatoxanthin

167

According to

168

Sargassum duplicatum and Undaria pinnatifida). Production of carotenoids by algae is

169

directly influenced by certain conditions such as; stress (alkaline pH, dark conditions), size of

170

the inoculum, intensity of light, the concentration of inorganic phosphates

171

birdiae is observed to produce Antheraxanthin and Alloxanthin whilst Euglenophyta,

172

Chlorarachniophyta, Chlorophyta and Codium fragile synthesized Loroxanthin and

173

siphonaxanthin, respectively 61,52, 62.

. Alloxanthin, crocoxanthin, monaxanthin (known as acetylenic carotenoids) are

59

and

60

55,56,57

. Red (Eucheuma isiforme etc) and

58,52

.

fucoxanthin can be extracted from brown algae (Sargassum binderi,

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. Gracilaria

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174

According to

, seagrasses are plants which are capable of flourishing along the coastlines

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(in both temperate and tropical) of the world. This helps in balancing the marine ecosystem

176

and biodiversity. The photosynthetic ability of the marine grasses is similar to that of

177

terrestrial plants because of different light exposure at variable depth hence constituting

178

carotenoid of different quantities and quality

179

different kinds of carotenoids (lutein,

180

siphonaxanthin) from Mediterranean seagrass species, Posidonia oceanica, Cymodocea

181

nodosa, Zostera noltii and Halophila stipulacea.

182

In another study, it was discovered that leaves of Cymodocea nodosa and Zostera marina,

183

contain seven photosynthetic carotenoids 66.

184

Galasso et al.

185

invertebrates exhibiting wide ranges of hues due to various carotenoids they contain. This

186

could be as a result of metabolic transformations and or from the feed they depend on.

187

Because naturally, they do not syntheses carotenoid de novo

188

sponges makes them brilliantly color

189

renierapurpurin) are predominant in sponges

190

contain Peridinin, pyrrhoxanthin, diadinoxanthin and Astaxanthin respectively 70,68.

191

Bivalves (oyster, clam, scallop, mussel, ark shell, etc.), sea slugs, sea snails and hare contains

192

lutein,

193

alloxanthin etc which originate from the food (microalgae) they consume. Some of these

194

animals are carnivores 71,72,73,74.

195

As stated by

196

(Tunicates) which includes ascidians. However, they can also originate as metabolites of

197

fucoxanthin, diatoxanthin, and alloxanthin biosynthesis. Marine animals show a structural

198

diversity of carotenoids such as β-carotene, fucoxanthin, peridinin, diatoxanthin, alloxanthin,

64,65

. Casazza and Mazzella

zeaxanthin,

violaxanthin,

65

extracted 6

neoxanthin and

48

, listed sponges, anemones, corals, jellyfishes and ascidians among marine

zeaxanthin,

75,73,76

fucoxanthin,

67

. Carotenoids present in

68

. Aryl carotenoids (isorenieratene, renieratene, and 69

. Some Corals and jellyfishes were found to

apocarotenoids,

diatoxanthin,

diadinoxanthin,

and

phytoplankton are the major sources of carotenoid for Protochordata

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and astaxanthin. These carotenoids are known to accumulate from the feed (algae and other

200

animals) these organism consumes. Through biotransformation, the marine organisms could

201

modify the various carotenoid in series of pathways.

202

Whale’s feeds on krill hence could accumulate astaxanthin. Octopus and cuttlefish were also

203

found to be a major source of astaxanthin. It is revealed that dolphin is a source of β-carotene

204

and lutein 77,78,68. Moreover, Salmonid fish and Perciformes, also accumulates esterifies form

205

of carotenoid in their tegument and gonads and lacks the necessary enzymes to synthesis

206

astaxanthin from other carotenoids but depend on crustacean zooplankton as sole source. The

207

bright yellow hues in the fins and skin of Perciformes are as a result of tunaxanthin 69,48. For

208

extensive review about carotenoid in marine animals reader is referred to 79,72,74,75,80,47,47.

209

2.2.2. Fungi

210

According to

211

Phycomycus blakesleeanus, and Choanephora cucurbitarum, and Rhodotorula aurea is

212

predominant sources of carotenoids. Industrial production of food colorant (β-carotene) is

213

mainly employed by B. trispora. Finkelstein et al. 82 patented their finding of how yield of β-

214

carotene is doubled when they employed B. trispora. β-carotene, γ-carotene, torulene, and

215

torularhodin are predominant carotenoids found in species of Rhodotorula and

216

Rhodosporidium

217

conditions (pH and concentration of salts and some amines) to impede proteins responsible

218

for cyclization of lycopene to β-carotene 84. An ultrasonic treatment of B. trispora resulted in

219

the production of 173 mg/L and 82 mg/L of β-carotene and lycopene respectively

220

increase in yield was observed in β-carotene from 44% to 65% and lycopene from 51% to

221

78% when n-hexane and n-dodecane were incorporated in the media. The addition of

222

antibiotics, natural oils, amino acids and vitamin A in culture media of B. trispora resulted in

223

significant increase in yield of β-carotene 86,87.

81

fungi and yeast such as Mucorales (Mucoromycotina), Blakeslea trispora,

83.

Lycopene can be synthesized by B. trispora by altering some media

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85

. An

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Xanthophyllomyces dendrorhous and Phaffia rhodozyma are predominant producers of

225

containing astaxanthin. However, X. dendrorhous is utilized for large-scale production of

226

astaxanthin

227

was successfully constructed by introducing the carotenogenic genes crtW (β-carotene

228

ketolase) and crtZ (β-carotene hydroxylase) into a β-carotene-producing

229

P. pastoris strain (Pp-EBIL) which was previously engineered 96,97.

230

P.

231

hydroxyechinenone, and phoenicoxanthin. Molecular tools like genetic engineering have also

232

been applied to alter carotenogenic genes for overexpression of lycopene, β-carotene, ζ -

233

carotene and astaxanthin 98,99,100.

234

According to

235

β-carotene, torulene, and torularhodin.

236

Also, other yeasts as Sporobolomyces salmonicolor and Sporobolomyces patagonicus are

237

carotenoids producers. A recent review published by

238

production of carotenoids taking into considerations the use of low-cost substrates (whey,

239

potato medium etc) from agro-industrial wastes as well as the factors influencing the

240

production. Valduga et al. 103 states that carotenoid synthesized by yeasts remain in the cells,

241

therefore additional cost must be incurred for the recovery resulting in high costs of

242

production.

243

2.2.3. Cyanobacteria

244

Cyanobacteria are capable of synthesizing numerous bioactive compounds including

245

carotenoids. These compounds are utilized by pharmaceutical companies as a template for

246

developing

247

myxoxanthophyll are found to be the predominant carotenoids produce by these

248

Cyanobacteria.

88-95

. Genetically-stable astaxanthin-producing P. pastoris strains (Pp-EBILWZ)

rhodozyma is also identified as produced carotenoids like echinenone, 3-

101

Sporobolomyces roseus (phylloplane yeasts) was discovered to synthesized

cancer

drugs.

Nevertheless,

β-carotene,

other

zeaxanthin,

carotenoids

102

outlines the microbial (yeast)

astaxanthin,

(ε-carotene,

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echinenone,

γ-carotene,

and

lycopene,

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104,105,106

. Gombos and Vig

107

249

canthaxanthin, oscillaxanthin) are also synthesized

observed

250

CrtQ and CrtP (homologous desaturase genes) to account for the synthesis of lycopene and ζ-

251

carotene, respectively. β-carotene (52%), zeaxanthin (38%), and small amounts of

252

caloxanthin, cryptoxanthin, and nostoxanthin were found to produce by Synechococcus sp.

253

(PCC7942).

254

Thermosynechococcus elongatus and Prochlorococcus marinus were found to be the

255

predominant producers of contains β-carotene and zeaxanthin. The strains also synthesize

256

nostoxanthin and α-carotene respectively. A significant volume of β-carotene was formed by

257

Trichodesmium sp., with retinyl palmitate esterase identified as the main enzymes responsible

258

for overexpression 108,109,31. Similar to algae, altering oxygen concentration and light intensity

259

could stimulate the production of these carotenoids. Cultivating Calothrix elenkenii under

260

lights resulted in significant increase in yield of β-carotene. Moreover, aerobic conditions

261

also favor the formation of β-carotene when Lyngbya sp. and Synechocystis sp. was cultured.

262

Irradiation or deletion of gene-altered the synthesis of canthaxanthin and β-carotene.

263

Synechocystis sp. was also found to produce zeaxanthin 110,106,31.

264

2.2.4. Bacteria

265

Nonphotosynthetic and nonphotosynthetic bacteria are found to produce major carotenoids

266

and details covered by

267

zeaxanthin,

268

thermozeaxanthins, nostoxanthin, caloxanthin, sarcinaxanthin, and staphyloxanthin are found

269

to be synthesized by numerous bacteria which has gained considerable attention due to its

270

sustainability, natural products and potential cost-effectiveness of this method. Microbial

271

production is widely accepted by consumers

272

which has attracted criticism. Metabolic engineering has been utilized to developed novel

273

Escherichia coli for producing carotenoid via fermentation. These strains produce a

111,112

astaxanthin,

. Carotenoids such as β-carotene, lycopene, canthaxanthin, α-bacterioruberin,

113-124

β-bacterioruberin,

deinoxanthin,

unlike the chemical method of synthesis

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125-

274

significant amount of carotenoids (i.e lycopene, β-carotene, zeaxanthin, and astaxanthin)

275

132,108,117

276

According to 133 species of Paracoccus was discovered to produce β-carotene, echinenone, β-

277

cryptoxanthin, canthaxanthin, astaxanthin, zeaxanthin, adonirubin, and adonixanthin.

278

Systems metabolic engineering has been applied to stimulate precursor compound

279

(isopentenyl diphosphate (IPP)) of carotenoid biosynthesis in E. coli of endogenous 2-C-

280

methyl-D-erythritol 4-phosphate (MEP) pathway or mevalonate (MVA) pathway. Among

281

five recombinant E. coli strains (MG1655, DH5α, S17-1, XL1-Blue, and BL21) compared,

282

DH5α was found to produce 465 mg/L of β-carotene.

283

Caloxanthin, zeaxanthin, and nostoxanthin was synthesized when CrtE, CrtB, CrtI, CrtY,

284

CrtZ, CrtX, from P. ananatis and CrtG from Brevundimonas SD212 were inserted into E. coli

285

134,123

286

sp. and Paracoccus zeaanthinifaciens. Bradyrhizobium sp., Agrobacterium aurantiacum and

287

Paracoccus carotinifaciens were found to accumulate high amount of canthaxanthin and

288

astaxanthin. Asker et al.

289

zeaxanthin and nostoxanthin.

290

Enterobacter species P41, and halobacteria (Halobacterium salinarium and Halobacterium

291

Sarcina) was observed to produce a significant amount of β-carotene and α-, β-

292

bacterioruberin, respectively

293

Staphylococcus aureus were identified to produce carotenoids like 4,4′-diaponeurosporene

294

and staphyloxanthin. S aureus is immune to oxidative stress because of staphyloxanthin.

295

Moreover, Since Staphyloxanthin is a membrane-bound carotenoid, it protects lipids but

296

might also be involved in protecting proteins and DNA. 139,140,141.

.

. According to

135

and

136

137

high titers of zeaxanthin was synthesized by Flavobacterium

reported pleomorphic bacterial strain (TDMA-16T) as producer

138,113

. Lactobacillus plantarum strain CECT7531 and

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Thermozeaxanthin, a rare carotenoid was extracted from Thermus thermophiles whereas

298

nostoxanthin and sarcinaxanthin were found to be synthesized in Erythobacter sp. and

299

Micrococcus luteus respectively 142,143,144.

300

2.3. Type of carotenoids

301

Carotenoids can be divided into three main categories, mainly based on presences or absent

302

oxygen (lutein Fig. 1D, violaxanthin, zeaxanthin, and α-cryptoxanthin), chemical structure

303

and others (Apocarotenoids, Homocarotenoids, Secocarotenoids, Norcarotenoids) (Fig 2)

304

Other classes of carotenoids are listed in Table 3. Currently, there are about 600 identified

305

carotenoids

306

violaxanthin, and siphonaxanthin) is the term assigned to carotenoids which contain oxygen

307

and separated from carotenes based on their polarity and are synthesized in the plastids. Also,

308

their synthesis does not require sunlight’s hence predominant in light-starved plants (young

309

and etiolated leaves). Nevertheless, carotenoids free of oxygen are called carotenes (lycopene

310

α-carotene, β-carotene) and are exclusively hydrocarbon. The oranges hue pigments are vital

311

for photosynthesis hence lights involving in the synthesis of carotene

312

carotenoids differ based on functional groups i.e hydroxyl and epoxy and are called

313

carotenols

314

homocarotenoids, and secocarotenoids are terms used to describe specific carotenoids

315

produced by an organism which differs based on number carbon atom 31.

316

Enzymatic and chemical (non-enzymatic) oxidative cleavage of carotenoids produces unique

317

biologically important carotenoid derivatives called apocarotenoids. It possesses the capacity

318

to inhibit mammalian cancer cell proliferation thus changing gene expression

319

removal of terminal methylene groups (CH3, CH2, or CH) from carotenoids results in the

320

formation of norcarotenoids which include 2,2′-dinor-β,β-carotene, and 12,13,20-trinor-β,β-

(lipid-soluble

and

epoxy

tetraterpenoids).

carotenoids,

Xanthophylls

respectively.

(zeaxanthin,

Apocarotenoids,

13 ACS Paragon Plus Environment

31

.

neoxanthin,

16

. Structurally,

norcarotenoids,

145,146

. The

Journal of Agricultural and Food Chemistry

31

. Sasaki et al.

147

321

carotene

isolated new norcarotenoids (trihydroxy-β-ionone and sec-

322

hydroxyaeginetic acid) from steamed roots of Rehmannia glutinosa var. hueichingensis.

323

Homocarotenoids (decaprenoxanthin) is exclusively synthesized by some bacterial organisms

324

where isoprene is introduced into C40 backbone (formed by more than eight units) 148,149.

325

Secocarotenoids is formed based on a triterpenoid, rather than the normal tetraterpenoid

326

backbone due to fission reaction

327

seeds of Pittosporum tobira.

328

2.4. Biosynthesis

329

Carotenoid biosynthesis is regulated throughout the life cycles of the plant, algae, fungi,

330

bacteria, and lichens with dynamic changes in composition matched to prevailing

331

developmental requirements and in response to external environmental stimuli. Basically, it

332

involves series of transformations which includes reactions, desaturation, cyclization,

333

hydroxylation, epoxidation, and epoxidefuranoxide rearrangement (Fig 3). Carotenoids

334

synthesis is catalyzed by 25 carotenogenic (Crt) genes. These proteins catalyze different

335

reactions. The precursors for the MEP-(glyceraldehyde-3-phosphate, pyruvate) and

336

mevalonate pathway (acetyl-CoA) respectively, as well as of cofactors, such as ATP and

337

NADPH are synthesized via glycolysis which is important for the formation of 5-carbon (C5)

338

isopentenyl-pyrophosphate (IPP) and dimethylallyl-pyrophosphate (DMAPP). Regulation of

339

MEP is possible by two enzymes mainly, 1-deoxyxylulose-5-phosphate synthase (DXS) and

340

1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), whereas mevalonate pathway is

341

catalyzed by AtoB, MvaA, MvaS, Mvak 1&2 and MvaD. A central intermediate

342

geranylgeranyl diphosphate (GGPP) is then synthesized, catalyzed by prenyl transferase

343

(CrtE). A 40-carbon phytoene is formed due to condensation of two GGPPs by phytoene

344

synthase (CrtB) 151-158,149.

31

. Maoka et al.

150

extracted three secocarotenoids from

14 ACS Paragon Plus Environment

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Page 15 of 84

Journal of Agricultural and Food Chemistry

345

Desaturation reaction (dehydrogenation) where double bonds are sequentially introducing at

346

the side of phytoene to form a 5 conjugated double bonds compound called phytofluene. ζ-

347

carotene (7 conjugated double bonds), neurosporene (9 conjugated double bonds), and finally

348

the pink-colored lycopene (11 conjugated double bonds). Depending on the species,

349

desaturation can be fulfilled by phytoene desaturase (CrtP), ζ-carotene desaturase (CrtQ) and

350

carotene isomerase (CrtH) in the case of plant and algae. In bacteria and fungi, phytoene

351

desaturase (CrtI) is responsible whereas in green sulfur bacteria 3 enzymes (CrtP, CrtQ, and

352

CrtH) catalyze the reaction 159-161.

353

Following

354

carotenoids. Transformation of acyclic lycopene is carried out by enzymes such as lycopene

355

cyclases, ԑ-cyclase, and β-cyclase to synthesize α- and β-carotene, respectively. CrtY, CrtL,

356

CruA, and CruP catalyzed the activities of lycopene cyclase. Carotenes (α- and β- carotene)

357

serves as precursors for carotenoids like xanthophylls, lutein, Zeaxanthin with the aid of β-

358

and є-ring specific hydroxylases (CrtG, CrtR) and β-ketolases (CrtO-mono ketolase, CrtW).

359

The activity of an enzyme violaxanthin de-epoxidase leads too introduction of an eposide

360

group to transform zeaxanthin to violaxanthin

361

apocarotenoids (i.e neurosporaxanthin) are able to synthesize by bacteria and fungi,

362

respectively. With the former and later catalyzed by enzymatic activities of lycopene

363

elongase and carotenoid oxygenase. Flavuxanthin serve as the precursor to synthesize

364

decaprenoxanthin by the action of ε-cyclase

365

carotenoids is produced yearly mainly lutein, violaxanthin, neoxanthin, and fucoxanthin

366

(predominant in macroalgae and microalgae) 164.

367

3. METHODS OF EXTRACTING CAROTENOIDS

368

3.1. Enzyme-base extraction

162

and

31

biogenesis pathways branches leading to the synthesis of various

47,16

. Homocarotenoids (i.e flavuxanthin) and

163,31

. It is estimated that about 108 tons/year of

15 ACS Paragon Plus Environment

Journal of Agricultural and Food Chemistry

369

Enzyme-base extraction method mainly depends on the selection of appropriate enzymes

370

(Pectinase, cellulase etc), optimum operational condition (temperature, pH, etc), and the

371

substrate (material). According to 165 the yield of lycopene increased up to 20 times higher as

372

compared to other methods via optimal enzyme concentration and process time. Enzymes

373

have the ability to destruct the structure of plant cells which houses the chloroplast membrane

374

from which the carotenoids are embedded

375

subsequently, plant materials utilized in extracting carotenoids require different enzymes for

376

effective destruction of cell walls in other to release carotenoid with cellular fluids. Table 4

377

shows carotenoids obtained from different sources with the aid of enzymes.

378

Merits of enzymatic extraction includes: 1) reduce extraction time; 2) enhance the

379

extractability/yield; 3) minimize the quantity of solvent involve in extraction/ in some

380

circumstance eliminate solvent totally, when vegetable oils are utilized as solvents; 4) it is

381

environmentally friendly and does not arouse criticism; 5) renewable (enzyme can be purified

382

and re-use). 6) relatively cheaper than organic solvents; 7) enzymes are flexible and specific;

383

8) many reactions can be achieved with a few enzymes. The main drawbacks of this method

384

are: enzymes are expensive to purchase, liable to degradation, and hence, care should be

385

adhered not to exceed the maximum operating temperature specified by the manufacturer.

386

Tomato tissue is composed of pectin, cellulose hemicellulose and enzymes applied has

387

pectinolytic, cellulolytic, hemicellulolytic activities respectively consequently enhanced the

388

extractability of lycopene 6 folds when compared to untreated sample 178.

389

Roberts 180 state that, the architecture of plant cell wall, constitute cellulose, a linear polymer

390

of β-1,4-linked glucose, and hemicelluloses, which forms a fairly rigid network that interacts

391

with a gel-like matrix of hydrated pectin substances. Degradation of this polysaccharide

392

creates a pore space for solvent penetration into the plant products inevitably improving the

393

efficiency and yield of carotenoids

166

. Each enzyme has a specific function

178

. Well documented literature review on application of

16 ACS Paragon Plus Environment

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Page 17 of 84

Journal of Agricultural and Food Chemistry

394

enzymes in the extraction of oil from sunflower and soybean, rapeseed, corn, coconut, olives,

395

avocado, including extraction of rice bran oil etc, has been revised by 181-185. Lucus et al. 177,

396

reported that the combined use of food-grade commercial plant cell-wall glycosidases

397

improved considerably the extraction of lycopene oleoresin from tomato matrix. The highest

398

titer (30.6 ± 2.1 mg cm-3) of lycopene of the hydrolyzed matrices was detected in treatment

399

with Celluclast/Novozyme + Viscozyme followed by Celluclast/Novozyme + Viscozyme +

400

Flavourzyme (30.1 ± 2.3 mg cm-3). However, Celluclast/Novozyme + Flavourzyme,

401

Celluclast/Novozyme, Viscozyme also gave better yield ( 21.2 ± 1.5, 18.1 ± 1.3 16.1 ± 1.5mg

402

cm-3 respectively) whereas the least titers were associated with Flavourzyme (8.7 ± 0.6 mg

403

cm-3) and the control (8.3 ± 0.8 mg cm-3).

404

Dominquez et al

405

enzymes to oilseeds during extraction of oil. Their work also pointed out the merit of using

406

enzyme over the conventional solvent methods which is generally problematic in terms of

407

efficiency and purity. Food industries have utilized these enzymes for decades, in

408

winemaking, brewing beer, starch processing, ripening cheese, the transformation of starch to

409

high fructose corn syrup and to obtain ferulic acid from sugar beet pulp

410

assessed the effects of different enzymes (cellulase, pectinase) concentration and time during

411

extraction of carotenoids from carrots, sweet potatoes, and orange peels. From the

412

experimental results, she concluded that maximum carotenoid yield was obtained by the

413

combination of 5 mL pectinase/100 g and 0.1 g cellulase/100 g in orange peels followed by

414

sweet potatoes (5 ml pectinase/100 g, 1 g cellulase/100 g for 12 and 18 h respectively. The

415

application of enzymes (pectinase and cellulase) destructed the cell wall of plant materials

416

(orange peels, sweet potatoes, and carrots) prompted the releases of carotenoids with other

417

water-soluble pigments. Barzana and colleague

418

Extraction to recover carotenoid from Tagetes erecta. They recorded 50% losses due to

182

reported an increased in yield and quality of oil when they applied

168

186

. Çinar

187

utilized enzyme-Mediated Solvent

17 ACS Paragon Plus Environment

Journal of Agricultural and Food Chemistry

Page 18 of 84

419

silaging, drying, and solvent extraction. It was recommended that addition of a substantial

420

volume of water for enzyme hydrolysis was unnecessary and should be avoided in further

421

works.

422

3.2. Supercritical fluid extraction (SFE)

423

The use of organic solvents in food processing has raised major public health, safety, and

424

environmental concerns. Thus, there are growing consumer concerns for the fear of solvent

425

residue remaining in final food and this warrants strict states regulation. One of the ideal

426

alternate extraction methods proposed to decrypt the above mention issues was the

427

supercritical fluid extraction (SFE) technology. Some fluids utilized includes carbon dioxide,

428

ethane,

429

chlorodifluoromethane, etc. Due to consumer concerns and other criticisms, water and carbon

430

dioxide could be used as traces of solvent in the end product is ruled out

431

properties of common solvents use in SCFE are detailed in

432

that supercritical carbon dioxide (SC-CO2), is the most preferred method of extracting

433

carotenoids (Natural products) for pharmaceuticals and food industries. Carbone dioxide is

434

noncorrosive,

435

environmentally friendly, and generally regarded as safe (GRAS).

436

SC-CO2 has been successfully applied in extracting carotenoids. Optimizing yield is the

437

function of many independent players, therefore, solvent flow rate, resident time, moisture

438

content, and particle size distribution in combination with supercritical pressures (Pc) and

439

temperatures (Tc) are crucial parameters to carefully adhere with. These parameters have

440

individual or combined effects on extractability (yield) of a particular plant material.

441

Consequently, modeling these parameters had been recently task in the scientific community

442

to decipher ways of optimizing yield

propane,

butane,

inert,

pentane,

inexpensive,

ethylene,

ammonia,

nonflammable,

192

sulfur

and

18 ACS Paragon Plus Environment

. Physical

. Rizvi et al.

odorless,

. Uquiche and his co-workers

water,

188-192

193

availability,

189

dioxide,

191

194

state

tasteless,

, modeled some

Page 19 of 84

Journal of Agricultural and Food Chemistry

443

parameters to optimize the yield of carotenoid pigments. Literature details of the model can

444

found in 195.

445

The solubility properties of the supercritical fluids are greatly affected by its density,

446

diffusivity, and viscosity (at a pressure of 5-50 MPa and temperature of 300°C)

447

literature reviewed by

448

solvents like acetone and chloroform.

449

Materials are loaded into the stationary phase via extraction column whilst extraction occurs

450

in the separation phase. SCFE utilizes compressed gases above their critical pressure (Tc) and

451

temperature (Tc). The solutes (carotenoids) are dissolved by these fluids in the solid bed for

452

harvesting. An investigation by 198 revealed that the direction of flow of SCF via a fixed bed

453

can be vertical or horizontal. Moreover, at high solvent ratios (ratio of the flow of SCFE to

454

the amount of solid material) the influence of gravity is insignificant. Bioactive compounds

455

i.e. antioxidants, flavonoids, lycopene, essential oils, lectins, carotenoids, etc, has

456

successfully been extracted from a variety of biological materials using the technology of

457

SCE

458

dealcoholize beverages, de-fat potato ships which are all found in our tables daily 198. Details

459

of the processes can be found in

460

tabulated by 192.

461

Merits of SC-CO2 overwhelm its demerits and are stated by

462

potentials similar to organic solvent and higher diffusivities; b) easier to control thus

463

separation can be altered by simply changing the operating pressure or temperature; c)

464

selective and separation power can be enhanced by modifying CO2 with co-solvents,

465

moreover solvating potentials could be extended to polar components; d) possibility of mild

466

extraction conditions combined with low energy requirements for solvent recovery 205.

197

196

. The

revealed the solubility potentials of CO2 is similar to that of

189

. This technology was applied to obtain vitamin additives, herbal medicine,

199-204

. Some known applications of SCFC technology are

19 ACS Paragon Plus Environment

189

, as; a) possessing salvation

Journal of Agricultural and Food Chemistry

Page 20 of 84

467

High capital investment and the complex operating system have limited the utilization of this

468

technology. Nevertheless, advocacy for SC-CO2 is on the rise due to recent advancement in

469

the equipment, processing, and demand for high-value products which are seen to be

470

profitable for processing industries 189.

471

Lycopene is susceptible to light, heat, oxygen, including acids and bases. When extracted

472

from tomatoes by SC-CO2 isomerization and degradation was minimized as compared with

473

conventional solvent extraction (CSE)

474

(Capsicum annuum L.) oleoresin by this technology

475

oleoresins are composed of light (e.g., fatty oils) and heavy constituents (e.g., pigments).

476

Uquiche et al.

477

(constituents) are extracted from the red pepper. An increased pressure from 320 to 550 bar

478

witnessed a significant extraction of the heavy component due to the excessive solubility at

479

high pressure. SC-CO2 extraction at 40oC is estimated to have a solubility of 1.2 mg/kg at 320

480

bar and 1.9 mg/kg at 540 bar, respectively whilst for lycopene (red carotenoid pigment in

481

tomato) it is estimated as 1.4 and 2.6 mg pigment/kg CO2 at 320 and 540 bar, respectively 209.

482

Durante et al.

483

from a pumpkin. Furthermore, the results were compared with CSE. They observed that SC-

484

CO2 resulted in much more efficient than CSE in terms of solid-liquid ratio, temperature,

485

extraction time and oil yield obtained. Nevertheless, the addition of co-matrix (milled

486

pumpkin) advanced yields.

487

The concentration of carotenoids in pepper determined by HPLC was doubled due to an

488

increase in extraction pressure (from 320 to 540 bar) which followed the trend of β-carotene

489

and lycopene solubility in SC-CO2 with pressure. Comparing the quantities of carotenoids

490

extracted and the utilization of SC-CO2 it can be estimated that, ≈0.9–2.9 mg pigment/kg CO2

491

was used. Thus recommending a solubility-controlled extraction of carotenoid pigments

191

206

. Carotenoids were also extracted from red pepper 191

. From literature

207,208

, red pepper

discovered that total carotenoid yield depends on how these fractions

210

, deal with the results acquired during the extraction oil rich in carotenoids

20 ACS Paragon Plus Environment

191

.

Page 21 of 84

Journal of Agricultural and Food Chemistry

492

The ratio of lycopene to β-carotenes increased with increasing pressure from 2.7 at 320 bar,

493

to 3.7 at 430 bar, and to 3.9 at 540 bar which goes to support the work of Uquiche and his

494

colleagues. Light red oleoresins (Lycopene) obtained was concentrated than that of the red

495

color (β-carotene) when extracted with SC-CO2 at 40oC and 320 bar, and at 40oC and 430 or

496

540 bar respectively (Table 5)

497

parameters (333.15 K, 29 MPa, and 1 mL CO2/min) and obtained the higher yield of β-

498

carotene 0.3524 g β-carotene/kg dry sample.

499

Multiple papers have been published on various aspects of optimizing conditions for SC-CO2

500

extraction of carotenoids 212-218.

501

According to

502

(60oC) it started to decline. Maximum yield was achieved at 300 and 500 bars in 39oC until

503

no further headway was observed on increased in temperature. The increase in yield was as a

504

result of complex interaction between density which decreased and prompted poorer

505

solvating potential. Productivity and cost viability of SCFE can be enhanced by applying

506

cosolvents (entrainers). Using 1-5% cosolvent can significantly change the properties of the

507

extraction fluid 189. The significant interaction between indirect-effect (cosolvent-solvent) and

508

direct-effect (cosolvent-solute) have been indicated by

509

189

510

SCF. Furthermore, they enhanced the selectivity of desired components and fractional

511

separation potentials. A previous work 220 utilized ethanol, methylene chloride, and methanol

512

in their work. It was found out that ethanol had the greatest enhancement factor whereas

513

methanol had the lowest. For more information on cosolvent in the SC-CO2 reader is referred

514

to pieces of literature, in particular,

515

purpose for which is been applied. An increase in solvent loading resulted in the co-

516

extraction of undesirable compounds

193

207,191

. Bashipour and Ghoreishi

211

optimized the following

an increase in temperature up to 46oC optimized yield of lutein but beyond

219

. From previous works of

192

and

, these changes significantly altered density and compressibility of original fluids used in

205,221-224

. Cosolvents should not hinder the specific

221

which contaminates target compounds (carotenoids

21 ACS Paragon Plus Environment

Journal of Agricultural and Food Chemistry

Page 22 of 84

517

etc). Functional properties and food formulated with this extracts (carotenoids) could be

518

altered due to these undesirable compounds. Nevertheless, SC-CO2 offers a novel approach in

519

extracting compounds of interest without traces of organic solvent.

520

Mongkholkhajornsilp et al.

521

SC-CO2. According to their results, the models helped in estimating the trend of extraction.

522

Models could be useful in optimizing yield since factors (mass transfer coefficient, co-

523

solvent, temperature, and pressure) could contribute negatively to the extraction process.

524

Moreover, experimental data gathered during extraction could be thus validated.

525

3.3. Microwave-assisted extraction (MAE)

526

MAE of carotenoids is unique in relation to traditional techniques – extraction occurs as a

527

result of changes in cell structure caused by electromagnetic waves

528

straightforward, quick and economic strategy for carotenoids extraction, requiring less

529

extraction time and low volume of solvents

530

Microwave extraction has been subdivided into microwave-assisted solvent extraction

531

(MASE) and microwave solvent-free extraction (MSFE). Due to denunciation by consumers

532

and ecologists, the latter is preferred.

533

MASE operates when materials (plants) and solvents (ethanol, methanol, Water) are mixed

534

and subjected to microwave energy, samples heats to a boiling point where the solvents

535

eventually enter into the plant materials. Target compounds (carotenoids) are then solubilized

536

and leached out. Samples absorbed heat via conduction and convection. Microwaves present

537

a controllable source of energy. Paré patented a technology known as the microwave-assisted

538

process (MAP), where the sample is first wet with solvents. By means of direct heating,

539

target compounds (carotenoid) escape from the sample matrix and drip into collecting flask.

540

The MAP has been successfully utilized in extracting oils and coloring agents for cosmetics

225

and

226

modeled extractions of ninbin from neem seed using

228,229

227

. This method is a

which reduces pollution and cost.

22 ACS Paragon Plus Environment

Page 23 of 84

Journal of Agricultural and Food Chemistry

541

and food industries. MASE requires less solvent and energy, thus receives fewer criticisms

542

than CSE 230-234.

543

Microwave hydro diffusion and gravity (MHG) also known as green extraction is a type of

544

MSFE which was developed for carotenoids extraction. This method depends on the “upside-

545

down” microwave alembic coupled with heating and earth gravity at atmospheric pressure for

546

its operation. It involves putting plant material in a microwave reactor, without solvents.

547

Microwaves from this reactor heat up plant cells and prompt the burst of oleiferous

548

repositories and organs, consequently freeing secondary metabolites (carotenoids) for

549

extraction via the perforated Pyrex disc. Due to the heating involved, a cooling system is

550

required outside the microwave oven for cooling the extract before harvesting

551

could curtail degradation and isomerization of carotenoids.

552

All-trans-lycopene was extracted by MAE utilizing ethyl acetate in solid to liquid ratio (20:1

553

(v/w), and power of 400 W for 1 min from tomatoes peels. The yield increased as the ratio

554

decreased by minimizing another solvent i.e- hexane whilst increasing ethyl acetate. Based

555

on the results, ethyl acetate was suggested as the right solvent than hexane in MAE due to its

556

high extract recovery. Despite the merits of MAE over CSE, degradation of carotenoids

557

cannot be ignored. However, the cooling system has been proposed outside this microwave

558

oven via the collection tubes to stabilize carotenoids

559

molecules occurs at the temperature of 60oC. Moreover, at this temperature, a phenomenon

560

known as thermooxidation occurs where hydrophobic carotenoids are oxidized into

561

hydrophilic carotenoids. Different extraction steps were studied and the results demonstrated

562

that more than one extraction step was needed to fully prompt the release of carotenoids from

563

paprika powders using either MAE or CSE. Notwithstanding, the results also indicate the

564

physiochemical properties of the solvents (cosolvent) should be factored in when calculating

565

the regression coefficient of MAE

237

. According to

238

235,230

, this

236

. Rearrangement of carotenoids

and

23 ACS Paragon Plus Environment

239

, the key factor in enhancing

Journal of Agricultural and Food Chemistry

566

the efficiency of extraction is the structure of plant materials. Therefore, pre-treatment of the

567

materials (chemical, biological and mechanical treatment) was the way forward in improving

568

carotenoids yield. Blanching carrots with water and citric as a treatment before MAE saw a

569

significant increase in yield of carotenoid and antioxidant activity than untreated samples.

570

The pre-treatment aided the destruction carrots cell wall consequently creating pores via

571

which carotenoids in the chloroplasts are leached out for extraction 238,229.

572

Application of intermittent microwave radiation coupled with MAE was utilized in extracting

573

carotenoids and β-carotene from carrot peels with varying parameters such as microwave

574

power (180 W or 300 W) and solvent volumes (75 or 150 mL) through increased diffusivity

575

of the solvent by increasing temperature

576

240

577

compounds from Adathoda vasica and Cymbopogon citratus. The yield of both methods was

578

similar, however, time spent to attain compounds via MAE and Soxhlet extraction was 210 s

579

and 10 h respectively. However, the yield of C. citratus by MAE was significantly higher

580

than SE when parameters were optimized (1:20 sample/solvent ratio, extraction time of 150 s

581

and 300 W output power). Thermal degradation has been pointed as one of the drawbacks

582

associating MAE as it reduces the bioavailability and health benefits of carotenoids. For this

583

reason, intermitted radiation as a better alternative for minimizing thermal degradation,

584

higher recovery and improved antioxidant activities of extracts was recommended 228.

585

3.4. Soxhlet extraction

586

Franz Von Soxhlet invented an extractor composed of thimble which houses plant materials

587

and is connected to a round bottom flask containing extraction solvent. When the solvent is

588

heated, the vapor travels via the distillation path of the extractor and then condense back onto

589

the plant materials. Via siphon exit, extract solvent/vapor falls back into the round bottom

590

flasks. The process is replicated until complete extraction is achieved. Degradation of target

228

. A two-step modeling approach was adopted by

, in their study to compare MAE and conventional Soxhlet extraction (SE) of bioactive

24 ACS Paragon Plus Environment

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Page 25 of 84

Journal of Agricultural and Food Chemistry

591

compounds was minimized by a condenser with running water attached to the extractor for

592

cooling. This technology is mostly applied to evaluate the efficiency of other conventional

593

techniques. Moreover, is suitable for extracting thermostable compounds because of the high

594

temperatures involved

595

sample mass than ME 245. Filtration is not obligatory when using SE. Moreover, it allows for

596

continuous extraction since there is constant contact between the sample and extracting

597

solvent. Nevertheless, it is not economical due to timing and requires large volumes of

598

extracting solvents.

599

As cited by

600

carotenoids due to high temperatures and prolong extraction time. For this reason, a modified

601

Soxhlet apparatus, aimed at overcoming the drawbacks of conventional Soxhlet extractor was

602

proposed by

603

magnesium and calcium silicates and polystyrenesulfonates [PSS] as absorbents via Soxhlet

604

extractor. Maximum carotenoids yield was obtained at 40-50 cycles with the aliquots. An

605

amount of 62.24%, 43.45%, 30.02% and 78.02% of carotenoids were extracted via Mg-

606

silicate, Ca-silicate, Mg-PSS and Ca-PSS absorbents respectively. Toluene was used to

607

stabilize extracted carotenoids. Yahaya also used this method to extract carotenes from carrot

608

with 2-propanol as extraction solvents 248. Solvents (n-hexane, ethanol, acetone, isopropanol,

609

and isopropanol: hexane) in a ratio of 50:50 v/v was utilized in the extraction of carotenoids

610

from pink shrimp (P. brasiliensis and P. paulensis) by-product after subjecting the samples to

611

pre-treatment (cooking, drying, milling). Different extraction methods were applied in

612

conjunction with Soxhlet extractor. From the results, it was uncovered that pre-treatment

613

significantly affected the yield. Furthermore, cooking broke the bond between carotenoid-

614

protein-complex. High yield of astaxanthin was obtained by Soxhlet with hexane:

615

isopropanol (21 ± 1 µgastaxanthin/g RM) and with acetone (20 ± 2 µgastaxanthin/g RM)

241-244,16

. SE assisted by ultrasound has the feasibility to extract more

229

, the high possibility of thermal degradation and cis-trans isomerization of

246

. Bangun et al.

247

extracted carotenoids from crude palm oil (CPO) using

25 ACS Paragon Plus Environment

249

. β-

Journal of Agricultural and Food Chemistry

Page 26 of 84

616

carotene was extracted from lyophilized skin powder of aloe vera by Soxhlet extractor,

617

petroleum ether as solvent (100 mL) and extraction time of 8 h 211.

618

3.5. Ultrasonic assisted extraction (UAE)

619

Ultrasound is waved ranged between 20 kilohertz (kHz) to several gigahertz (GHz).

620

Commercial application of UAE has witnessed global acceptance, process improvements,

621

maintenance cost drastically reduced

622

requirement is comparatively low than other industrial equipment though this depends on the

623

application. As cited by

624

extraction due to acoustic cavitation destroying cell walls releasing carotenoids and water-

625

soluble pigments out of the cells.

626

Maximum betacyanin (1.42 ± 0.001 mg/g) and betaxanthin (5.35 ± 0.13 mg/g) were obtained

627

from Basella rubra. L using UAE with extraction temperature (54°C), ultrasonic power (94

628

W), extraction time (32 min) and solid to liquid ratio (1:17 g/mL)

629

colleague coupled UAE with intermittent radiations, to extract carotenoids from carrot

630

residue. Maximum β-carotene at 83.32% and 64.66% was obtained via ultrasound irradiation

631

and ultrasonic bath respectively, the solvent with medium vapor pressure, low viscosity, and

632

surface tension performed best 253.

633

A cheaper, simple-to-use technique of carotenoids extraction was developed by 255 (termed:

634

green UAE). Maximum β-carotene (334.75 mg/l) was achieved in 20 min with sunflower oil

635

as the solvent and CSE gave (321.35 mg/l) at 60 min. Goula et al.

636

carotenoid from pomegranate peels. It was revealed that maximum yield was achieved at the

637

extraction temperature, 51.5oC; peels/solvent ratio, 0.10; amplitude level, 58.8%; solvent,

638

sunflower oil. In summary, using sunflower oil as a solvent in UAE will approximately

639

extract 85.7-93.8% of carotenoids in materials moreover, it is environmentally friendly

252

253

and

250

. Pingret et al.

251

reported that the energy

utilization of UAE to enhanced yield and efficiency of

26 ACS Paragon Plus Environment

256

254

. Purohit and his

optimized yields of

Page 27 of 84

Journal of Agricultural and Food Chemistry

640

Ultrasound and magnetic stirring methods were compared by 257, during extraction of natural

641

dye from carrot. UAE gave better yield because ultrasound assisted the mass transfer via the

642

solvent. Luo

643

microemulsions. The results showed altered process kinetics and improved yield of

644

ginsenoside at 20 kHz, 15.2 Wcm−2, and 3/6 s. Kumcuoglu et al.

645

conventional organic solvent extraction (COSE) when they extracted lycopene from tomatoes

646

waste. Solvents used included hexane: acetone: ethanol (2:1:1) with 0.05% (w/v) butylated

647

hydroxytoluene (BHT). The maximum yields were obtained at the liquid-solid ratio of 35:1

648

(v/w) with an ultrasonic power of 90 W whereas in COSE 50:1 (v/w) liquid-solid ratio, 40

649

min extraction time and 60°C temperature gave the best results. The authors also noted that

650

each parameter applied in both methods significantly affected the yield.

651

4. Saponification

652

Application of carotenoids in food and pharmaceutical industries requires quantification. But

653

carotenoids are extracted with other undesirable compounds (lipids, fatty acids, chlorophylls)

654

which are embedded in the cell components. These undesirable compounds could interfere

655

with equipment readings giving false results. For this reason, saponification is practiced to

656

eliminated compounds which could destruct any analytical readings of equipment ie

657

Ultraviolet-Visible spectrophotometry (UV-Vis), high-performance liquid chromatography

658

(HPLC), high-performance thin layer chromatography (HPTLC), nuclear magnetic resonance

659

(NMR), thin layer chromatography (TLC), Fourier transform infrared spectroscopy (FTIR)

660

and ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS).

661

According to

662

hence must be eliminated. Carotenoids like carotene, exist in free form whereas xanthophylls

663

are acylated with saturated and unsaturated fatty acids. This esterified xanthophylls with

664

other undesirable substances can contribute to a false reading on chromatograms 261,229, which

258

, extracted ginsenosides using UAE in supercritical CO2 reverse

260

259

compared UAE with

carotenoids are esterified in materials (fruits/vegetables) by fatty acids,

27 ACS Paragon Plus Environment

Journal of Agricultural and Food Chemistry

Page 28 of 84

665

is not accepted in the scientific community. Effective saponification was achieved with 2%

666

methanolic KOH (w/v) after 6 hours beyond which degradation started to occur

667

Extraction and saponification also preferably should be carried out separately as this gave

668

better results. Saponification was shown to increase recovery of β-carotene and lutein

669

Based on the raw material, saponification can also lead to losses of carotenoids. For instance,

670

264

671

saponification. Similar results were obtained by 265,266 when they could not recover sufficient

672

β-carotene from table olives.

673

Granado et al.

674

hydroxide, hexane/methylene chloride extraction) protocol of saponification. The results

675

confirmed the ''shortcut'' saponification was accurate like the standard protocol. Moreover,

676

the shortcut was cheaper, easier to perform, many samples can be treated, and operation is

677

carried out at standard room temperature. Saponification is encouraged when working with

678

lipid-rich samples 267. Saponification is less applied to extract which are meant for cosmetics

679

industries.

680

5. Health concerns with carotenoids intake

681

There have been several reports about carotenoid having some links with cancer and other

682

ailments. This call for a serious concern and researchers and funding bodies have already

683

responded to this challenge. A simple search on known databases without restriction using

684

the keyword like ''carotenoid intake cancer risk'' resulted in about 38300, 1110, 761, and 913

685

for Google Scholar, Scopus, Web of Science, Pumped respectively. Table 6 shows recent

686

works about health concerns on carotenoids.

687

Conversion of β-carotene to retinol was altered due to excessive alcoholism. In another study,

688

alcohol addicts had higher risk of lung cancer (RR = 1.16; 95% CI = 1.02-1.33; p = 0.02,

689

logrank test) when supplemented with high-dose β-carotene

262

.

263

.

, registered 20-30%, 50% loss of β-carotene and other carotenoids respectively due to

266

developed ''shortcut'' (small volumes, vortex 3 min, 20% potassium

28 ACS Paragon Plus Environment

281-283

. Heavy smokers had the

Page 29 of 84

Journal of Agricultural and Food Chemistry

690

higher chance of developing lung cancer when supplemented with 20 or 30 mg/day of β-

691

carotene

692

lovastatin

693

appropriately when taken along with carotenoids (β-carotene). Moreover, intake of β-

694

carotene with vitamins and selenium suppressed some beneficial effects of niacin.

695

Cholesterol levels increased as niacin interacted with carotenoids

696

carried a comparative study with β-carotene and lutein in ratios of 2:1 and 1:2, respectively.

697

The results revealed lutein had inhibitory effect when it was the predominant carotenoid. In

698

plasma serum studies, β-carotene exerted an inhibitory effect over lutein. The evidence of

699

carotenoid interaction was observed by

700

carotene and xanthophylls (lutein). A decrease in Vitamin A deposition in liver was observed

701

at low β-carotene and xanthophylls (lutein) ratio (1). Canthaxanthin was also reported to have

703

altered β-carotene absorption 289.

704

A strong inverse association with pancreatic cancer risk was established during higher dietary

705

intake of antioxidants including selenium, vitamin C, vitamin E, β-carotene and β –

706

cryptoxanthin 290. Lu and colleague made contradictory findings in their research. Intake of a-

707

carotene, b-carotene, β-cryptoxanthin, and lycopene was inversely associated with colorectal

708

cancer risk. However, no significant association was found with lutein/zeaxanthin intake and

709

colorectal cancer risk 269.

710

Umesawa et al.

711

minimizing the risk of prostate cancer among the Japanese population. This is in agreement

712

with results obtained by several authors 291,268,292,293.

713

Hayhoe et al. 294, carried out a cohort study about Carotenoid dietary intakes and osteoporotic

714

fracture risk. The results showed that carotenoids were all inversely associated with hip

284

. Cholesterol-lowering drugs like atorvastatin (Lipitor), fluvastatin (Lescol),

(Mevacor),

276

and

pravastatin

288

(Pravachol)

could

not

metabolize/function

285,286

. Van den Berg

287

when the rat was fed with different ratios of β-

states that moderate to high α-carotene intakes might contribute to

29 ACS Paragon Plus Environment

Journal of Agricultural and Food Chemistry

Page 30 of 84

715

fracture risk in men, and significantly, associations were identified for women. This goes to

716

support previous work 295.

717

Lung cancer was notice to decrease due to an intake of β-carotene, α-carotene, β-

718

cryptoxanthin, lycopene, and vitamin C

719

support the findings. However, high intakes of lutein/zeaxanthin did not significantly lower

720

the risk of lung cancer as reported by 398-302.

721

According to

722

to have the highest prostate cancer incidence rates compared with other racial groups. This

723

finding should be an automatic call for Africa as a continent to start researching on these

724

especially with carotenoids. However, throughout our research, we could not come across a

725

single research that is carried out in Africa. We are, therefore, taking this opportunity to alert

726

the Africa Union and the countries within it to consider funding such research for the

727

betterment of its citizens and the world as a whole.

728

6. Conclusion

729

Carotenoids are not thermostable compounds hence liable to heat, light, oxygen which could

730

cause degradation and, isomerization. Consequently, laboratory environment should be

731

controlled. However, encapsulation could also help curb/minimize the interaction between

732

extracted carotenoids and environmental factors. Therefore, we recommend for rapid

733

encapsulation of freeze-dried carotenoids immediately after extractions. With respect to

734

methods of extraction, SC-CO2 and enzyme-based showed the best results in regard to both

735

product and process safety on the environment. Coupling two or more methods could also

736

enhance yield, reduce cost, and time of extraction in some cases. In addition, response

737

surface methodology could be applied for optimizing extractions parameters for better yields.

738

For the enzymatic method of extraction, knowledge about the cell structure of the particular

739

plant material is very important. Vegetable oils could also replace chemical solvents. Heavy

296

. A recent meta-analysis conducted by

297

goes to

304

, African-American (AA) men and African-Caribbean (AC) men are known

30 ACS Paragon Plus Environment

Page 31 of 84

Journal of Agricultural and Food Chemistry

740

smokers and alcoholics should either minimize/quit when they are on carotenoid supplements

741

to avoid being exposed to the risk of chronic diseases mentioned above. However, this could

742

also ensure efficient metabolism of carotenoids to confer health benefits.

743

Abbreviations

744

SC-CO2, supercritical carbon dioxide; UAE, Ultrasonic assisted extraction; MAE,

745

Microwave-assisted extraction; MASE, microwave-assisted solvent extraction; MSFE,

746

microwave solvent-free extraction; SFE, Supercritical fluid extraction; COSE, conventional

747

organic solvent extraction; UV-Vis, Ultraviolet-Visible spectrophotometry; HPLC, high-

748

performance liquid chromatography; HPTLC, high-performance thin layer chromatography;

749

NMR, nuclear magnetic resonance;

750

transform infrared spectroscopy, UPLC-MS, ultra-performance liquid chromatography-

751

tandem mass spectrometer, TCP, thermodynamic critical points; GRAS, generally regarded

752

as safe; DXS, 1-deoxyxylulose-5-phosphate synthase; DXR, 1-deoxy-D-xylulose 5-

753

phosphate reductoisomerase; UV, ultraviolet.

754

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755

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1592 1593 1594 1595 1596 1597 1598 1599 1600

Figure1. Molecular structures of various carotenoids; (A) Canthaxanthin, (B) Lycopene, (C)

1601

Astaxanthin, (D) Lutein.

1602

Figure 2. Classification of carotenoids

1603

Figure 3. An overview of biosynthetic pathways of carotenoids in plant, algae,

1604

cyanobacteria,

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pyrophosphate/GGPP= Geranyl geranyl pyrophosphate; G3P= glyceraldehyde-3-phosphate;

1606

HMG-CoA= 3-hydroxy-3- methyl-glutaryl-CoA; MEP=Methylerythritol 4-phosphate.

and

bacteria.

IPP=

Isopentyl

pyrophosphate;

1607 1608 1609 1610 1611 1612 1613 1614 1615 1616 1617 1618 1619 1620 1621 1622 1623 1624 1625 66 ACS Paragon Plus Environment

FPP=

Farnesyl

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1626 1627 1628 1629 1630 1631 1632 1633 1634 1635 1636 1637 1638 1639 1640 1641

A

1642 1643

B

1644 1645 1646

C

1647 1648 1649

D

1650 1651 1652 1653

Figure.1 Molecular structures of various carotenoids; (A) Canthaxanthin, (B) Lycopene, (C) Astaxanthin, (D) Lutein.

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1654 1655

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Figure 2. Classification of carotenoids. Adapted with permission from Stephen NM et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization eds. Siddiqui MW, Bansal V, and Prasad K. , and Kamlesh Prasad, PhD, © 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondary-metabolitesvolume-2-stimulation-extraction-and-utilization/9781771883542

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Figure 3. An overview of biosynthetic pathways of carotenoids in plant, algae, cyanobacteria, and bacteria.

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Adapted with permission from Ref. 4333401464437 (John Wiley and Sons, 2016) and Stephen NM et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization eds. Siddiqui MW, Bansal V, and Prasad K. , and Kamlesh Prasad, PhD, © 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondary-metabolites-volume-2-stimulationextraction-and-utilization/9781771883542.

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Table 1. Carotenoids Content in Major Plant. Table 2. Microbial sources of carotenoids. Table 3. Classes of Carotenoids Based on Their Structure, and the Presence of Functional Group. Table 4. Carotenoids extracted from different plant materials using enzymes. Table 5. Concentration of carotenoid pigments in red pepper oleoresins obtained with SC-CO2. Table 6. Studies on carotenoid intake and health concerns.

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Table 1. Carotenoids Content in Major Plant.

Sources

Carotenoids

Carrot (raw) Carrot (cooked) Pumpkin Winter Squash (Butternut) Plantains (raw) Banana (raw) Balsam-pear (raw) Carrot (raw) Carrot (cooked) Mango Mango canned Sweet potato cooked Pumpkin canned Peppers (raw) Pepper (cooked) Okra Apricots Asparagus Tomato (raw) Tomato (cooked) Tomato paste Tomato sauce Tomato soup Tomato juice Watermelon Papaya Pink grapefruit Pink guava Gac Mandarin oranges Tangerine Papaya Orange juice Spinach Broccoli Lettuce Green peas Watercress Maize Mandarin oranges Red pepper

α-carotene

β-carotene

Lycopene

β-Cryptoxanthin

Lutein

Zeaxanthin

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Quantity-wet weight based (mg/100g) 5.00 3.70 2.72 1.13 0.72 0.29 2.18 18.30 8.00 2.15 13.10 9.50 6.90 2.40 2.20 0.18 3.82 1.19 3.00 4.40 29.30 15.90 10.90 9.30 4.90 3.40 0.03 0.05 2-3 1.77 1.60 0.47 1.98 6.26 2.26 1.25 1.84 10.71 0.44 0.14 0.60

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Yellow bell pepper Violaxanthin 4.40 Spinach 2.80 Creamed spinach 2.50 Beko (Oroxylum indicum) 0.10 Beluntas (Pluchea indica) 0.06 Cekur manis (Sauropus 0.12 androgynu) Mengkudu (Morinda 0.03 citrifolia) Paraga (Centella asiatica) 0.08 Arugula Neoxanthin 1.00 Leek 1.00 Lamb’s lettuce 0.90 Paraga (Centella asiatica) 0.03 Mengkudu (Morinda 0.13 citrifolia) Cekur manis (Sauropus 0.09 androgynu) Adapted with permission Stephen NM et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization eds. Siddiqui MW, Bansal V, and Prasad K., and Kamlesh Prasad, PhD, © 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondary-metabolites-volume-2-stimulationextraction-and-utilization/9781771883542,16,17 .

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Table 2. Microbial sources of carotenoids. Carotenoids Astaxanthin

β-Carotene

α-Carotene

Algae, seagrasses and marine animals Haematococcus pulvialis, Chlorococcum sp., Chlorella zofingiensis, Chlorella vulgaris, Botryococcus braunii, Thraustochytrid strain KH105, Arbacia lixula, Charonia sauliae, starfish, holoturians, crabs, shrimp, lobsters, shellfish, Whales

Botryococcus braunii, Dunaliella salina, Gracilaria birdiae, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea, shellfish, sea urchin, starfish, holoturians, dolphin

Fungi/yeast Xanthophyllomyces dendrorhous, Peniophora sp., Phaffia rhodozyma, Thraustochytrium strains ONC-T18 and CHN-1, Thraustochytriidae sp. AS4-A1, Aurantiochytrium sp. KH105 Blakeslea trispora, Phycomycus blakesleeanus, Choanephora cucurbitarum, Rhodotorula aurea, Rhodosporidium diobovatum, Aspergillus giganteus, Sporobolomyces roseus Rhodotobacter sphaeroides, Rhodotorula glutinis Rhodotorula acheniorum Rhodotorula mucilaginosa, 74 ACS Paragon Plus Environment

Cyanobacteria

Bacteria Agrobacterium aurantiacum, Paracoccus Carotinifaciens, Paracoccus sp. strain DSM 11574.

Synechococcus sp., Thermosynechococcus elongates, Prochlorococcus marinus, Trichodesmium sp., Calothrix elenkenii, Synechocystis sp., Lyngbya sp.

Prochlorococcus marinus

Enterobacter sp. strain P41 Paracoccus sp. strain DSM 11574

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Zeaxanthin

Lutein

Lycopene Vialoxanthin

Neoxanthin

Diatoxanthin

Fucoxanthin

Nannochloropsis oculata, Chaetoceros gracilis, Dunaliella salina, Porphyridium cruentum, Gracilaria damaecornis, Macrocystis pyrifera, Botryococcus braunii, Gracilaria birdiae Muriellopsis sp., Chlorella protothecoides, Eucheuma isiforme, Chlorella zofingiensis, Coccomyxa acidophila, Scenedesmus almeriensis, Botryococcus braunii, dolphin Haloarchaea Chlorophyta, Botryococcus braunii, Gracilaria birdiae, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea Chlorophyta, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea Heterokontophyta, Haptophyta, Dinophyta, Euglenophyta. Undari pinnatifida, Heterokontophyta, Sargassum binderi, Sargassum

Synechococcus sp., Thermosynechococcus elongates

Blakeslea trispora

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Flavobacterium sp., Paracoccus zeaanthinifaciens

Journal of Agricultural and Food Chemistry

duplicantum, Odontella aurita, Phaeodactylum tricornutum, Isochrysis aff. Galbana, Laminalia japonica, Hijikia fusiformis, Undaria pinnatifida, Laminaria japonica, Alaria crassifolia, Cladosiphon okamuranus, Cystoseira hakodatensis, Eisenia bicyclis, Hijikia fusiformis, Ishige okamurae, Kjellmaniella crassifolia, Myagropsis myagroides, Padina tetrastromatica, Petalonia binghamiae Siphonaxanthin Loroxanthin

Antheraxanthin

Alloxanthin Torulene and torularhodin

Neurosporoxanthin

Codium fragile Euglenophyta, Chlorarachniophyta, Chlorophyta Gracilaria birdiae, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea Gracilaria birdiae Rhodotorula minuta, Rhodosporidium sp., Verticillium agaricinum, Sporobolomyces roseus Neurospora crassa, 76 ACS Paragon Plus Environment

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Echinenone, phoenicoxanthin Myxol Mytiloxanthin Caloxanthin Nostoxanthin

Gonads of sea urchin

Canthaxanthin

Haloferax alexandrines, Thraustochytrid strain KH10, Dietzia natronolimnaea HS-1

Fusarium sp., Verticillium sp., Podospora anserine, Giberella fujikuroi, Phycomyces blakesleanus Phaffia rhodozyma

tunicates, mussels and oysters Synechococcus sp. Synechococcus sp., Thermosynechococcus elongatus

Erythobacter sp.

Bradyrhizobium sp., Paracoccus sp. strain DSM 11574

Cryptoxanthin Adonirubin, adonixanthin α- and βbacterioruberin

Staphyloxanthin Peridinin

Paracoccus sp. strain DSM 11574 Flavobacteriaceae

Synechococcus sp. Paracoccus sp. strain DSM 11574 Halobacterium salinarium, Halobacterium sarcina Staphylococcus aureus

Heterocapsa Symbiodinium, sulcate, pliciferum

triquetra, Anemonia Amaroucium

Thermozeaxanthin Halocynthiaxanthin sea squirt and sea pineapple

Thermus thermophilus

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and Fuxoxanthinol

(e.g., Halocynthia roretzi), Paracentrotus lividus

Deinoxanthin

Deinococcus radiodurans Sarcinaxanthin Micrococcus luteus β-cryptoxanthin Paracoccus sp. strain DSM 11574 Modified with permission from Stephen NM et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization eds. Siddiqui MW, Bansal V, and Prasad K. , and Kamlesh Prasad, PhD, © 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondary-metabolites-volume-2-stimulationextraction-and-utilization/9781771883542, 48

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Table 3. Classes of Carotenoids Based on Their Structure, and the Presence of Functional Group. Apocarotenoids Presence/absence of oxygen Presence of oxygen Absence oxygen α-Carotene α-Cryptoxanthin Antheraxanthin Antheraxanthin α-Carotene Retinol ζ-Carotene β-Carotene β-Cryptoxanthin Astaxanthin Auroxanthin β-Carotene Bixin, Phytoene δ-Carotene Auroxanthin Lutein Luteoxanthin γ-Carotene Crocin Lycopene γ-Carotene Canthaxanthin Rubixanthin Neoxanthin δ-Carotene Apo-8′-β-carotenal Neurosporene Lycopene Capsanthin Zeaxanthin Violaxanthin α-Zeacarotene Apo-8′-lycopenal Phytofluene Neurosporene Capsorubin Zeinoxanthin Fucoxanthin Mycorradicin Prolycopene β-Zeacarotene Phytoene α-Crypoxanthin Fucoxanthinol Flavoxanthin Tethyatene Cachloxanthin 1,2Phytofluene Siphonaxanthin β-Cryptoxanthin Mutatoxanthin Galloxanthin Dihydrolycopene Torulene α-Zeacarotene Crocetin Alloxanthin Renieratene Cryptoflavin Sinensiaxanthin Rhodopin β-Zeacarotene Lutein Diatoxanthin Isorenieratene Latoxanthin Persicachrome Chloroxanthin Parasiloxanthin Luteoxanthin Chlorobactene Salmoxanthin Sinensiachrome Lycoxanthin Lycophyll Nostoxanthin Renierapurpurin Dinoxanthin Valenciaxanthin Spirilloxanthin Lycoxanthin Loroxanthin Diadinoxanthin Cochloxanthin Neoxanthin Lutein-5,6-epoxide Saproxanthin micropteroxanthins Rubixanthin Caloxanthin β-Carotene-5,6Tunaxanthin Crustaxanthin epoxide Violaxanthin Nigroxanthin β-Carotene-5,8Zeaxanthin Rhodopinol epoxide Lactucaxanthin Zeinoxanthin Gobiusxanthin Salmonxanthin Adapted with permission from Stephen NM et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization eds. Siddiqui MW, Bansal V, and Prasad K. , and Kamlesh Prasad, PhD, © 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondary-metabolites-volume-2-stimulationextraction-and-utilization/9781771883542,68 Acyclic carotenes

Chemical structure Cyclic carotenes Epoxy-carotenoids

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Table 4. Carotenoids extracted from different plant materials using enzymes. Reference Source Carotenoids Enzymes used % increase in yield over conventional method Marigold Lutein Cellulase, 2–5 fold increase 167,168 hemicellulase pectinase 0.01–0.1 %w/w 169 Chilli carotenoids Cellulase, carotenoid-11 170 and hemicellulase, Capsaicin-7 capsaicin Pectinase 171 Carrot Carotenes Pectinase, cellulase 41–49 172

173

Carrot spent

Carotenes

174

Tomato

Lycopene

175,176

Olives

177

Tomato Tomato Tomato Tomato

177 177 177

177

Tomato

177

Tomato

167

Marigold Marigold Marigold Marigold Marigold Tagetes erecta Tagetes erecta

167 167 167 167 168 168

168

Tagetes erecta

168

Tagetes erecta

178

Marigold Flowers Marigold Flowers

178

Pectinase + hemicellulose Pectinase, cellulose

Chlorophyll Pectinase + Carotenoids hemicellulose Lycopene Celluclast/Novozyme Lycopene Viscozyme Lycopene Flavourzyme Lycopene Celluclast/Novozyme + Viscozyme Lycopene Celluclast/Novozyme + Flavourzyme Lycopene Celluclast/Novozyme + Viscozyme + Flavourzyme Carotenoids Rapidase-Press Carotenoid Pectinase-Cep Carotenoids Econase-cep Carotenoid Cytolase-0 Carotenoids Cytolase-m129 Carotenoids Viscozyme Carotenoids Viscozyme + HTProteolytic Carotenoids Viscozyme + HTProteolytic + Pectinex Carotenoids Viscozyme + HTProteolytic (silaged flower) Carotenoids Cellulase 0.5 mL/100 g Carotenoids Cellulase + Hemicellulase + Pectinase 0.5mL/100 g-0.2g/100 80 ACS Paragon Plus Environment

_

20 _

18-22 18-22 18-22 ~153 44-67 44-67

_ _ _ _ _ ~85 ~90 ~98 ~100

_

_

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g-0.5 mL/100 g Cellulase + Hemicellulase + _ Pectinase 0.8mL/100 g-0.4g/100 g-0.8 mL/100 g 179 Tomato pastes Lycopene Citrozym Ultra L ~40 179 Tomato pastes Lycopene Peclyve LI ~85-90 179 Tomato pastes Lycopene Peclyve EP ~75-80 179 Tomato pastes Lycopene Citrozym C ~65-70 Adapted with permission from Ref. 4345950156258 (Taylor & Francis, 2010), 177,178,179 178

Marigold Flowers

Carotenoids

Table 5. Concentration of carotenoid pigments in red pepper oleoresins obtained with SCCO2. Pigment concentration (g carotenoid pigment/kg SC-CO2 oleoresin) 330 bar 430 bar 540 bar HPLC analysis Total concentration 3.65 7.01 7.66 Total concentration of red 2.66 5.53 6.08 pigments Capsorubin 0.21 0.89 1.10 Capsanthin 0.75 0.84 0.91 Capsanthin 5,6 epoxide 0.39 1.33 1.04 Zeaxanthin 0.94 2.08 2.41 Cryptocapsin 0.37 0.39 0.62 Total concentration of 0.99 1.48 1.58 yellow pigments β-Cryptoxanthin 0.35 0.83 0.89 β-Carotene 0.64 0.65 0.69 Spectrophotometric analysis 20.1 27.0 31.6 (total concentration) Adapted with permission from Ref. 4333390128071 (Elsevier, 2004),191.

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Table 6. Studies on carotenoid intake and health concerns. Design Carotenoids involved Year

Cohort Study

Hospital based case-control

Hospital-based case-control study Cohorts study

Cross-sectional study

A Case– Control Study Case-Control Study

α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, βcryptoxanthin α-carotene, β-carotene, lutein/zeaxanthin, lycopene, and βcryptoxanthin α-carotene, β-carotene, lutein/zeaxanthin, lycopene, βcryptoxanthin β-cryptoxanthin, lycopene, lutein & zeaxanthin, sum of all carotenoids β-cryptoxanthin, lycopene, lutein plus zeaxanthin, β-carotene and α-carotene Carotenes Lycopene, α-carotene, β-carotene, βcryptoxanthin, lutein, and zeaxanthin

Location

Carotenoid Intake assessment Questionnaire

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Type of health concern

Reference

268

1986-2006

The Netherlands

2010

China

Food frequency questionnaire

Colorectal cancer

585

269

1992-2008

Italy

Questionnaire

Nasopharyngeal carcinoma

792

270

1993–1997 merged in 2007

The Netherlands

Food frequency questionnaire

Type 2 diabetes

37846 (915 )

271

2011

Brazil

Food frequency questionnaire

DNA damage (lipid oxidation and)

296

272

2013-2016

China

273

Vietnam

Primary liver cancer Prostate Cancer

644

2013–2015

Food frequency questionnaire Food-frequency questionnaire

652

274

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Head and Neck Cancer

Sample size (Incidence recorded) 5000

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β-carotene

2013-2014

Australia

Food Frequency Questionnaire

Skin Yellowness

31

275

α-carotene β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene

1989-2009 2001–2006

Japan USA

Prostate cancer Prostate cancer

15 471 (143) 134

276

Cohorts study

β-carotene

2007

Finland

Questionnaire Phase 1: Clinical trial. Phase 2:Intervieweradministered questionnaires Questionnaires

29,133

278

Cohorts study

β-carotene, α-carotene, lutein, β-cryptoxanthin, lycopene α-carotene, β-carotene, lycopene, lutein/zeaxanthin

1988-1990, and 1992

USA

Food-frequency questionnaire

Aerodigestive tract cancers Prostate cancer.

47894 (812)

279

1986-1992

The Netherlands

Food frequency questionnaire,

Prostate cancer

58279 (642)

Randomized controlled crossover trial Cohorts study Cross-sectional study

Cohort Study

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277

28

Journal of Agricultural and Food Chemistry

TOC Graph:

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