Chapter 1 Introduction to Polyketide Biosynthesis. Weissman, K. J. In volume 459, of Complex Enzymes in Microbial Natural Product Biosynthesis, Part B: Polyketides, Aminocoumarins and Carbohydrates, pages 3--16. Academic Press, 2009. ![Chapter 1 Introduction to Polyketide Biosynthesis [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper abstract bibtex Even among natural product-derived medicines, the polyketides stand out. The fungal-derived statins are the most successful cardiovascular drugs of all time. Erythromycin A, a macrolide antibacterial, has been in clinical usage for 53 years, while its semisynthetic derivative azithromycin (Zithromax) is one of the best-selling antibiotics in the world. The enediynes, relative newcomers to the polyketide stage, are among the most powerful anticancer agents yet discovered. More than a third of natural product and natural product-derived compounds approved as drugs in the 2005–2007 period were polyketides, while a host of others are advancing through clinical trials. As testimony to their importance, annual sales of polyketide-derived medicines routinely top US\$20 billion. The endless variety of polyketide shape and structure continues to fascinate synthetic and natural product chemists alike. However, the biochemical basis for programming alternative modes of polyketide construction to yield polyketones, partially reduced polyketides or fully reduced fatty acids, remained obscure; no obvious mechanism was available to explain the choice or number of building blocks and the order in which they are incorporated, the extent of redox adjustment following each round of chain extension, and the pattern of cyclization or lactonization of the resulting chains. The answer to this conundrum has emerged over several decades through sequencing and biochemical studies of hundreds of genes encoding for polyketide synthases (PKSs) and associated decorating enzymes; conveniently, these biosynthetic genes are often clustered together within the genomes of the producing organisms.
@incollection{weissman_chapter_2009,
series = {Complex {Enzymes} in {Microbial} {Natural} {Product} {Biosynthesis}, {Part} {B}: {Polyketides}, {Aminocoumarins} and {Carbohydrates}},
title = {Chapter 1 {Introduction} to {Polyketide} {Biosynthesis}},
volume = {459},
url = {http://www.sciencedirect.com/science/article/pii/S0076687909046011},
abstract = {Even among natural product-derived medicines, the polyketides stand out. The fungal-derived statins are the most successful cardiovascular drugs of all time. Erythromycin A, a macrolide antibacterial, has been in clinical usage for 53 years, while its semisynthetic derivative azithromycin (Zithromax) is one of the best-selling antibiotics in the world. The enediynes, relative newcomers to the polyketide stage, are among the most powerful anticancer agents yet discovered. More than a third of natural product and natural product-derived compounds approved as drugs in the 2005–2007 period were polyketides, while a host of others are advancing through clinical trials. As testimony to their importance, annual sales of polyketide-derived medicines routinely top US\$20 billion. The endless variety of polyketide shape and structure continues to fascinate synthetic and natural product chemists alike. However, the biochemical basis for programming alternative modes of polyketide construction to yield polyketones, partially reduced polyketides or fully reduced fatty acids, remained obscure; no obvious mechanism was available to explain the choice or number of building blocks and the order in which they are incorporated, the extent of redox adjustment following each round of chain extension, and the pattern of cyclization or lactonization of the resulting chains. The answer to this conundrum has emerged over several decades through sequencing and biochemical studies of hundreds of genes encoding for polyketide synthases (PKSs) and associated decorating enzymes; conveniently, these biosynthetic genes are often clustered together within the genomes of the producing organisms.},
urldate = {2016-08-11TZ},
publisher = {Academic Press},
author = {Weissman, Kira J.},
editor = {Enzymology, BT - Methods in},
year = {2009},
pages = {3--16}
}
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Erythromycin A, a macrolide antibacterial, has been in clinical usage for 53 years, while its semisynthetic derivative azithromycin (Zithromax) is one of the best-selling antibiotics in the world. The enediynes, relative newcomers to the polyketide stage, are among the most powerful anticancer agents yet discovered. More than a third of natural product and natural product-derived compounds approved as drugs in the 2005–2007 period were polyketides, while a host of others are advancing through clinical trials. As testimony to their importance, annual sales of polyketide-derived medicines routinely top US\\$20 billion. The endless variety of polyketide shape and structure continues to fascinate synthetic and natural product chemists alike. However, the biochemical basis for programming alternative modes of polyketide construction to yield polyketones, partially reduced polyketides or fully reduced fatty acids, remained obscure; no obvious mechanism was available to explain the choice or number of building blocks and the order in which they are incorporated, the extent of redox adjustment following each round of chain extension, and the pattern of cyclization or lactonization of the resulting chains. 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