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bioRxiv · 10.1101/509463

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

Liang, H.·Jiang, L.·Jiang, Q.·Shi, J.·Xiang, J.·Yan, X.·Zhu, X.·Zhao, L.·Shen, B.·Duan, Y.·Huang, Y.
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Abstract

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 {beta}-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 inhouse 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.

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Liang, H., Jiang, L., Jiang, Q., Shi, J., Xiang, J., Yan, X., Zhu, X., Zhao, L., Shen, B., Duan, Y., Huang, Y.. 2019-01-02. A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases. https://doi.org/10.1101/509463

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