NEWS OF THE WEEK
CO2H
HALOGENATION IN THE GARDEN SYNTHETIC BIOLOGY: Chemists
integrate carbon-halogen bond formation into plant metabolism
B
Y ENGINEERING a popular garden plant to ex-
press halogenase enzymes from soil bacteria, a team of Massachusetts Institute of Technology researchers has expanded the plant’s ability to biosynthesize complex natural products to include making rare halogenated analogs. The development could make it easier to produce desirable halogenated pharmaceuticals in plants rather than in engineered bacteria or by way of elaborate multistep chemical syntheses. Weerawat Runguphan and Sarah E. O’Connor previously engineered the Madagascar periwinkle, Catharanthus roseus, to convert exogenous halogenated tryptamines into halogenated alkaloids. Runguphan, O’Connor, and Xudong Qu now report that they have engineered the plants to make the halogenated tryptamines themselves (Nature, DOI: 10.1038/nature09524). The researchers overexpressed bacterial RebH or
CHEMICAL PROFITS REBOUND IN JAPAN FISCAL FIRST HALF: Demand
is strong for all materials
M
AJOR JAPANESE chemical firms posted a
sharp improvement in earnings in the first half of the fiscal year that ends on March 31, 2011. Companies that recorded losses a year ago are now profitable. Japanese companies said they experienced strong export demand across all their product lines, mostly from customers based in other Asian countries. Demand was particularly strong for electronic materials, and Mitsubishi Chemical reported healthy demand for its petrochemical products as well. Companies noted that demand from the U.S. and Japan remains weak. Despite boosting its net earnings by more than five times compared with a year ago, Asahi Kasei said it has been facing a “particularly challenging” environment because of the slowing U.S., Japanese, and Chinese economies. In contrast, the profit margin at Shin-Etsu Chemical soared to nearly 12% after net earnings increased by 75%. Although demand for polyvinyl chloride resins in the U.S. was weak, Shin-Etsu was able to find buyers in
PyrH halogenase enzymes, which work with a partner reductase, RebF, to selectively chlorinate tryptophan in the 7-position or 5-position, respectively. The plant’s natural tryptophan decarboxylase enzyme takes over to convert the chlorotryptophan to chlorotryptamine, which is shuttled into the plant’s alkaloid biosynthetic pathway where it is fused with the monoterpene secologanin. This intermediate is further functionalized to yield various chlorinated alkaloids in plant cell cultures. With RebH, the process can also produce brominated analogs. The report by O’Connor’s group “represents a crowning achievement to rationally engineer the biosynthesis of unnatural chlorinated alkaloids,” says Bradley S. Moore of Scripps Institution of Oceanography. “While this type of metabolic reengineering is now commonplace in microbial systems, it is unprecedented in more complex higher organisms.” Earlier this year, Moore’s group collaborated with David O’Hagan’s group at Scotland’s University of St. Andrews to clone the first fluorinase gene from a soil bacterium into a marine bacterium to produce a fluorinated analog of the anticancer compound salinosporamide. “We are in an exciting new phase in metabolite engineering,” O’Hagan says. “It is clear that the tools are developing to selectively halogenate natural products by biotechnological, rather than chemical, methods.”— STEVE RITTER
NH2 N H Tryptophan 1. RebH, RebF 2. Tryptophan decarboxylase
NH2 N H
Cl
7-Chlorotryptamine Secologanin
N
Cl
H CO2CH3
N H
Chlorinated dihydroakuammicine
other parts of the world. The company said it enjoyed strong global demand for another one of its core products, 12-inch silicon wafers. Sumitomo Chemical also enjoyed strong demand for its electronic materials, which are mostly used in the manufacture of liquid-crystal displays. Whereas Sumitomo had recorded an operating loss in its electronics segment one year ago, the business achieved profits of more than $150 million in the past six months. Despite the business improvements, Sumitomo achieved overall net earnings of only $30 million in the fiscal first half because of a sharp drop in the valuation of its 20% stake in Nufarm, an Australian producer of generic agrochemicals.—JEAN-FRANÇOIS TREMBLAY
JAPAN’S FIRST HALF Profits improved substantially at Japanese chemical firms
$ MILLIONS
Asahi Kasei JSR Kaneka Mitsubishi Mitsui Shin-Etsu Sumitomo Teijin
SALES CHANGE 2010 FROM 2009
$9,156 2,039 2,685 18,732 8,055 6,376 11,843 4,787
16.1% 18.3 11.1 36.6 22.4 27.6 34.6 11.0
EARNINGSa
PROFIT MARGINb
2010
2009
2010
$341 159 75 526 205 746 30 138
$51 -5 48 -31 -376 425 -42 -309
3.7% 7.8 2.8 2.8 2.5 11.7 0.3 2.9
2009
0.6% def 2.0 def def 8.5 def def
NOTE: Monetary figures were calculated at the Sept. 30 exchange rate of $1.00 = 83.53 yen. a Aftertax earnings including exceptional items. b After-tax earnings as a percentage of sales. def = deficit.
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