Insights into Azalomycin F Assembly-line Contribute to Evolution-guided Polyketide Synthase Engineering and Identification of Intermodular Recognition

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Feb 4

PMID 36739290

Authors

Guifa Zhai

Yan Zhu

Guo Sun

Fan Zhou

Yangning Sun

Zhou Hong

Chuan Dong

Peter F Leadlay

Kui Hong

Zixin Deng

Fuling Zhou

Yuhui Sun

Affiliations

Soon will be listed here.

Abstract

Modular polyketide synthase (PKS) is an ingenious core machine that catalyzes abundant polyketides in nature. Exploring interactions among modules in PKS is very important for understanding the overall biosynthetic process and for engineering PKS assembly-lines. Here, we show that intermodular recognition between the enoylreductase domain ER inside module 1/2 and the ketosynthase domain KS inside module 3 is required for the cross-module enoylreduction in azalomycin F (AZL) biosynthesis. We also show that KS of module 4 acts as a gatekeeper facilitating cross-module enoylreduction. Additionally, evidence is provided that module 3 and module 6 in the AZL PKS are evolutionarily homologous, which makes evolution-oriented PKS engineering possible. These results reveal intermodular recognition, furthering understanding of the mechanism of the PKS assembly-line, thus providing different insights into PKS engineering. This also reveals that gene duplication/conversion and subsequent combinations may be a neofunctionalization process in modular PKS assembly-lines, hence providing a different case for supporting the investigation of modular PKS evolution.

Citing Articles

Evolution-guided engineering of -acyltransferase polyketide synthases.

Mabesoone M, Leopold-Messer S, Minas H, Chepkirui C, Chawengrum P, Reiter S Science. 2024; 383(6689):1312-1317.

PMID: 38513027 PMC: 11260071. DOI: 10.1126/science.adj7621.

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