Navigating the fungal polyketide chemical space: From genes to molecules

Heng Chooi, Y. Tang

Research output: Contribution to journalReview article

118 Citations (Scopus)

Abstract

The iterative type I polyketide synthases (IPKSs) are central to the biosynthesis of an enormously diverse array of natural products in fungi. These natural products, known as polyketides, exhibit a wide range of biological activities and include clinically important drugs as well as undesirable toxins. The PKSs synthesize these structurally diverse polyketides via a series of decarboxylative condensations of malonyl-CoA extender units and β-keto modifications in a highly programmed manner. Significant progress has been made over the past few years in understanding the biosynthetic mechanism and programming of fungal PKSs. The continuously expanding fungal genome sequence data have sparked genome-directed discoveries of new fungal PKSs and associated products. The increasing number of fungal PKSs that have been linked to their products along with in-depth biochemical and structural characterizations of these large enzymes have remarkably improved our knowledge on the molecular basis for polyketide structural diversity in fungi. This Perspective highlights the recent advances and examines how the newly expanded paradigm has contributed to our ability to link fungal PKS genes to chemical structures and vice versa. The knowledge will help us navigate through the logarithmically expanding seas of genomic information for polyketide compound discovery and provided opportunities to reprogram these megasynthases to generate new chemical entities. © 2012 American Chemical Society.
Original languageEnglish
Pages (from-to)9933-9953
JournalJournal of Organic Chemistry
Volume77
Issue number22
DOIs
Publication statusPublished - 2012

Fingerprint

Polyketides
Genes
Molecules
Biological Products
Fungi
Polyketide Synthases
Malonyl Coenzyme A
Biosynthesis
Bioactivity
Condensation
Enzymes
Pharmaceutical Preparations

Cite this

@article{383f7a75a9984edb8deac7f275a33bf2,
title = "Navigating the fungal polyketide chemical space: From genes to molecules",
abstract = "The iterative type I polyketide synthases (IPKSs) are central to the biosynthesis of an enormously diverse array of natural products in fungi. These natural products, known as polyketides, exhibit a wide range of biological activities and include clinically important drugs as well as undesirable toxins. The PKSs synthesize these structurally diverse polyketides via a series of decarboxylative condensations of malonyl-CoA extender units and β-keto modifications in a highly programmed manner. Significant progress has been made over the past few years in understanding the biosynthetic mechanism and programming of fungal PKSs. The continuously expanding fungal genome sequence data have sparked genome-directed discoveries of new fungal PKSs and associated products. The increasing number of fungal PKSs that have been linked to their products along with in-depth biochemical and structural characterizations of these large enzymes have remarkably improved our knowledge on the molecular basis for polyketide structural diversity in fungi. This Perspective highlights the recent advances and examines how the newly expanded paradigm has contributed to our ability to link fungal PKS genes to chemical structures and vice versa. The knowledge will help us navigate through the logarithmically expanding seas of genomic information for polyketide compound discovery and provided opportunities to reprogram these megasynthases to generate new chemical entities. {\circledC} 2012 American Chemical Society.",
author = "Heng Chooi and Y. Tang",
year = "2012",
doi = "10.1021/jo301592k",
language = "English",
volume = "77",
pages = "9933--9953",
journal = "The Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "22",

}

Navigating the fungal polyketide chemical space: From genes to molecules. / Chooi, Heng; Tang, Y.

In: Journal of Organic Chemistry, Vol. 77, No. 22, 2012, p. 9933-9953.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Navigating the fungal polyketide chemical space: From genes to molecules

AU - Chooi, Heng

AU - Tang, Y.

PY - 2012

Y1 - 2012

N2 - The iterative type I polyketide synthases (IPKSs) are central to the biosynthesis of an enormously diverse array of natural products in fungi. These natural products, known as polyketides, exhibit a wide range of biological activities and include clinically important drugs as well as undesirable toxins. The PKSs synthesize these structurally diverse polyketides via a series of decarboxylative condensations of malonyl-CoA extender units and β-keto modifications in a highly programmed manner. Significant progress has been made over the past few years in understanding the biosynthetic mechanism and programming of fungal PKSs. The continuously expanding fungal genome sequence data have sparked genome-directed discoveries of new fungal PKSs and associated products. The increasing number of fungal PKSs that have been linked to their products along with in-depth biochemical and structural characterizations of these large enzymes have remarkably improved our knowledge on the molecular basis for polyketide structural diversity in fungi. This Perspective highlights the recent advances and examines how the newly expanded paradigm has contributed to our ability to link fungal PKS genes to chemical structures and vice versa. The knowledge will help us navigate through the logarithmically expanding seas of genomic information for polyketide compound discovery and provided opportunities to reprogram these megasynthases to generate new chemical entities. © 2012 American Chemical Society.

AB - The iterative type I polyketide synthases (IPKSs) are central to the biosynthesis of an enormously diverse array of natural products in fungi. These natural products, known as polyketides, exhibit a wide range of biological activities and include clinically important drugs as well as undesirable toxins. The PKSs synthesize these structurally diverse polyketides via a series of decarboxylative condensations of malonyl-CoA extender units and β-keto modifications in a highly programmed manner. Significant progress has been made over the past few years in understanding the biosynthetic mechanism and programming of fungal PKSs. The continuously expanding fungal genome sequence data have sparked genome-directed discoveries of new fungal PKSs and associated products. The increasing number of fungal PKSs that have been linked to their products along with in-depth biochemical and structural characterizations of these large enzymes have remarkably improved our knowledge on the molecular basis for polyketide structural diversity in fungi. This Perspective highlights the recent advances and examines how the newly expanded paradigm has contributed to our ability to link fungal PKS genes to chemical structures and vice versa. The knowledge will help us navigate through the logarithmically expanding seas of genomic information for polyketide compound discovery and provided opportunities to reprogram these megasynthases to generate new chemical entities. © 2012 American Chemical Society.

U2 - 10.1021/jo301592k

DO - 10.1021/jo301592k

M3 - Review article

VL - 77

SP - 9933

EP - 9953

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

SN - 0022-3263

IS - 22

ER -