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The Catalytic Diversity of Multimodular Polyketide Synthases: Natural Product Biosynthesis Beyond Textbook Assembly Rules

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Topics in Current Chemistry

Part of the book series: Topics in Current Chemistry

Abstract

Bacterial multimodular polyketide synthases (PKSs) are responsible for the biosynthesis of a wide range of pharmacologically active natural products. These megaenzymes contain numerous catalytic and structural domains and act as biochemical templates to generate complex polyketides in an assembly line-like fashion. While the prototypical PKS is composed of only a few different domain types that are fused together in a combinatorial fashion, an increasing number of enzymes is being found that contain additional components. These domains can introduce remarkably diverse modifications into polyketides. This review discusses our current understanding of such noncanonical domains and their role in expanding the biosynthetic versatility of bacterial PKSs.

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Abbreviations

A:

Adenylation domain

ACL:

Acyl-CoA ligase

ACP:

Acyl carrier protein

ACS:

Acyl-CoA synthetase

AHBA:

3-Amino-5-hydroxybenzoic acid

AL:

Acyl-[ACP] ligase

AMP:

Adenosine monophosphate

AMT:

Aminotransferase

AS:

Acyl-[ACP] synthetase

AT:

Acyltransferase

ATP:

Adenosine triphosphate

C:

Condensation domain

CLF:

Chain length factor

CoA:

Coenzyme A

CP:

Carrier protein

CR:

Crotonase

CY/CYC:

Cyclase

DEBS:

6-Deoxyerythronolide B synthase

DH:

Dehydratase

DUF:

Domain of unknown function

ECH:

Enoyl-CoA hydratase

ER:

Enoylreductase

ESI:

Electrospray ionization

FAS:

Fatty acid synthase

FT-ICR-MS:

Fourier-transform ion cyclotron mass spectrometry

GNAT:

GCN5-related N-acetyltransferase

H:

Hydrolase

Hal:

Halogenase

HMG:

3-Hydroxy-3-methylglutaryl

HMGS:

3-Hydroxy-3-methylglutaryl-CoA synthase

KR:

Ketoreductase

KS:

Ketosynthase

KS0 :

Nonelongating ketosynthase

KSQ :

Decarboxylating ketosynthase of a PKS loading module

LC:

Liquid chromatography

MS:

Mass spectrometry

MT:

Methyltransferase

NMR:

Nuclear magnetic resonance (spectroscopy)

NRPS:

Nonribosomal peptide synthetase

OMT:

O-Methyltransferase

PAPS:

Phosphoadenosine-5′-phosphosulfate

PCP:

Peptidyl carrier protein

PKS:

Polyketide synthase

PLP:

Pyridoxal 5′-phosphate

PMP:

Pyridoxamine 5′-phosphate

PPTase:

Phosphopantetheinyl transferase

R:

Reductase

ST:

Sulfotransferase

TE:

Thioesterase

UV:

Ultraviolet

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Acknowledgments

This work was supported by the DFG (SFB 642 to J.P. and M.F.F.) and a re-integration fellowship of the DAAD to T.A.M.G.

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  1. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, 53121, Bonn, Germany

    Tobias A. M. Gulder, Michael F. Freeman & Jörn Piel

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Gulder, T.A.M., Freeman, M.F., Piel, J. (2011). The Catalytic Diversity of Multimodular Polyketide Synthases: Natural Product Biosynthesis Beyond Textbook Assembly Rules. In: Topics in Current Chemistry. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2010_113

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