Book Review Cite This: J. Nat. Prod. XXXX, XXX, XXX−XXX
pubs.acs.org/jnp
Review of Natural Product Biosynthesis: Chemical Logic and Enzymatic Machinery amino acids, formation of unique functional groups in peptides, non-proteinogenic amino acids, and PKS and NRPS assembly lines. The chapter on terpenes highlights the particularities of mevalonate and of methylerythritol pathways, including mechanisms, the promiscuity of terpene cyclases, and biosynthetic steps of physiologically and therapeutically relevant sterols, as well as the importance of carotene formation and its derivatives. Hybrid biosynthesis of PKSterpenoids and alkaloid-terpenoids is also presented in this chapter. The alkaloid chapter describes the formation of major alkaloid classes, mainly in plants but also in fungi (indolederived and anthranilate-derived) and bacteria (indolocarbazoles). Classical examples of plant aromatic, pyrrolizidine, piperidine, and steroidal alkaloids are included. Only a few examples of fungal and bacterial alkaloids are mentioned in this chapter, since a separate chapter on indole-terpene alkaloids is included later. The contextualization of purine and pyrimidine alkaloids in relation to DNA and RNA synthesis and expression is very interesting. The biosynthesis of highly modified purines and pyrimidines is discussed, with many examples from plants and bacteria. The chapter on phenylpropanoids relates secondary metabolites with the production of lignin and lignans, illustrating the role of the major enzymes and biosynthetic steps in the formation of modified and dimerized lignans, as well as in the formation of hybrid metabolites, such as feruloyl derivatives, chalcones, stilbenes, flavonoids, phytoalexins, and coumarins. A section describing the formation of plastoquinones and tocopherols is also included. The second chapter on alkaloids is directed to discuss the biosynthesis of indole terpenes, involving Pictet−Spengler and other cyclization reactions as observed for β-carbolines, roquefortines, physostigmines, and unusual and modified diketopiperazines. Indole prenylation and subsequent modifications are discussed in detail, mostly for fungal metabolites. Additional examples include Vinca alkaloids, bacterial indole terpenes, lyngbyatoxins, and cyclopiazonic acids. The two chapters on structural biology and enzyme mechanisms present the formation of carbon−carbon bonds, mediated by free-radical intermediates. Pathways showing the participation of iron complexes, co-factors, and heme-based cytochromes are well discussed and illustrated in the biosynthesis of distinct metabolites. A sub-topic on halogenases is also included, showing the versatility of oxidases and oxygenases in generating chemical diversity in secondary metabolites. The chapter on S-adenosyl methionine presents an excellent discussion on methylation and carbon−carbon bond formation mediated by SAM, by both ionic and radical processes.
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Natural Product Biosynthesis: Chemical Logic and Enzymatic Machinery. By Christopher T. Walsh and Yi Tang. Royal Society of Chemistry Publishing. 2017. xx + 765 pp. £89.00 (∼$119). ISBN 978-1-78801-076-4.
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his is a long-awaited book since the advent of molecular biology tools for the investigation of secondary metabolism in the 1980s. A complete monograph addressing the biosynthesis of natural products (secondary metabolites) at the genetic and enzymatic level did not exist, although several books presented specific topics on the biosynthesis of natural products based on such approaches. Walsh’s and Tang’s work assembles the fundamental knowledge of modern approaches for the investigation of the biosynthesis of natural products, resulting in a textbook. The book is organized in four sections. Section I, “Introduction to Natural Products”, comprises a single chapter in which the authors provide an overview of the major classes of natural products and a brief presentation on how these compounds are biosynthetically constructed. Section II, “Six Natural Products Classes”, is divided into seven chapters that include a detailed discussion on the formation of polyketides, peptides, isoprenoids, alkaloids, purines and pyrimidines, phenylpropanoids, and indole terpenes. Section III describes the structural biology, function, and mechanisms of “Key Synthetic Enzymes in Natural Product Biosynthetic Pathways”, including oxygenases and S-adenosyl methionine (SAM). Included in the same section, Chapter 11, covering glycosylation of metabolites, presents a slightly different structure, with emphasis on glucosides’ diversity and glycosylation mechanisms. In Section IV, “Genome-independent and Genome-dependent Detection of Natural Products”, the two main approaches for the discovery of natural products are summarized and discussed in two chapters. While the authors did not attempt to present a comprehensive content, a task nearly impossible to perform, the examples selected provide an excellent overview of the major achievements on the biosynthesis investigation of secondary metabolites in the post-genomic era. The book includes the primary literature up to 2016 from key researchers who have advanced the field. The book illustrates the evolving biosynthetic experimental techniques starting with the use of radioactive precursors, moving on to the advent of nuclear magnetic resonance detection, and ending with modern molecular and structural biology tools. The steps of biosynthesis of the major classes of natural products are explained in very clear detail. The chapters devoted to the biosynthesis of polyketides and peptides include an array of examples. Particular sections include the formation of aromatic moieties in fungal and bacterial metabolites, macrolactonization, cyclizations via cycloadditions, formation of polyethers, formation of unique structural groups in peptides such as thiazoles/oxazoles and their reduced derivatives, formation of C−C bonds between © XXXX American Chemical Society and American Society of Pharmacognosy
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DOI: 10.1021/acs.jnatprod.8b00451 J. Nat. Prod. XXXX, XXX, XXX−XXX
Journal of Natural Products
Book Review
The chapter on oligosaccharides and glycosides provides an excellent overview on the formation of aminoglycoside antibiotics, modified sugars, distinct glycosylation mechanisms, and the importance of sugars for specific groups of natural products. These include the major aminoglycosides, several polyglycosidic compounds, plant hormones, glycosylated macrolactones, sterols and steroids, flavonoids and derivatives, anthracyclins, indolocarbazoles, vancomycin and derivatives, and cyanogenic glycosides, among others. The two final chapters provide a summary of the major experimental approaches for the discovery and investigation of natural products. Chapter 12 mentions historical, economically and medicinally relevant examples of plant and microbial metabolites, including contemporary top-down approaches such as OSMAC, real-time mass spectrometry, and target screenings. Chapter 13 presents a summary of gene cluster analysis, bioinformatics and computational predictions, and heterologous expression, with examples from plant and bacterial kingdoms. The Walsh and Tang book is a pleasure to read, even considering its substantial amount of information. Drawings are mostly clear, a few of which are rather small, probably due to space limitations. Only a few mistakes have been found in the text and figures. Examples of biosynthesis investigations coming from the marine environment or from insects are not abundant, but this certainly is not a drawback for this outstanding contribution that assembles a voluminous amount of information. It should be considered as essential for all those interested in better understanding how natural products are assembled from biochemical precursors, complementary to Paul Dewick’s Medicinal Natural Products and McMurry and Bengley’s The Organic Chemistry of Biological Pathways. This is a highly recommended book for advanced undergraduate and graduate students, as well as for established investigators, interested in learning details on the astonishing metabolic diversity of the biosynthesis of natural products.
Roberto G. S. Berlinck
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Universidade de São Paulo, Sao Carlos, Brazil
AUTHOR INFORMATION
ORCID
Roberto G. S. Berlinck: 0000-0003-0118-2523 Notes
The author declares no competing financial interest.
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DOI: 10.1021/acs.jnatprod.8b00451 J. Nat. Prod. XXXX, XXX, XXX−XXX
