Issue 1, 2017

Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis

Abstract

Actinobacteria produce a variety of polyketide alkaloids with unusual structures. Recently, it was shown that a type I modular polyketide synthase (PKS) is involved in the assembly of coelimycin P1, a polyketide alkaloid produced by Streptomyces coelicolor M145. However, the mechanisms for converting the product of the PKS to coelimycin P1 remain to be elucidated. Here we show that the C-terminal thioester reductase (TR) domain of the PKS and an ω-transaminase are responsible for release of the polyketide chain as an aldehyde and its subsequent reductive amination. Bioinformatics analyses identified numerous gene clusters in actinobacterial genomes that encode modular PKSs with a C-terminal TR domain and a homolog of the ω-transaminase. These are predicted to direct the biosynthesis of both known and novel polyketide alkaloids, suggesting that reductive chain release and transamination constitutes a conserved mechanism for the biosynthesis of such metabolites.

Graphical abstract: Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis

Supplementary files

Article information

Article type
Edge Article
Submitted
24 iyn 2016
Accepted
21 avq 2016
First published
22 avq 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2017,8, 411-415

Author version available

Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis

U. R. Awodi, J. L. Ronan, J. Masschelein, E. L. C. de los Santos and G. L. Challis, Chem. Sci., 2017, 8, 411 DOI: 10.1039/C6SC02803A

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