DOI: 10.1101/509463Jan 2, 2019Paper

A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases

BioRxiv : the Preprint Server for Biology
Haoyu LiangYong Huang


Acyltransferase (AT)-less type I polyketide synthases (PKSs) produce complex natural products due to the presence of many unique tailoring enzymes. The 3-hydroxy-3-methylglutaryl coenzyme A synthases (HCSs) are responsible for β-alkylation of the growing polyketide intermediates in AT-less type I PKSs. In this study, we discovered a large group of HCSs, closely associated with the characterized and orphan AT-less type I PKSs through in silico genome mining, sequence and genome neighborhood network analysis. Using HCS-based probes, the survey of 1207 in-house strains and 18 soil samples from different geological locations revealed the vast diversity of HCS-containing AT-less type I PKSs. The presence of HCSs in many AT-less type I PKSs suggests their co-evolutionary relationship. Our study should inspire future efforts to discover new polyketide natural products from AT-less type I PKSs.

Related Concepts

DNA Probes
Polyketide synthase
AN 3
Biotin-[acetyl-CoA-carboxylase] Ligase Activity
Natural Products
Chemical Probe

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