Issue 45, 2022

Discovery of pentaene polyols by the activation of an enediyne gene cluster: biosynthetic implications for 9-membered enediyne core structures

Abstract

The identification and characterization of enediyne polyketide synthases (PKSEs) revealed that PKSE-bound polyene is a common intermediate, while its subsequent tailoring steps to enediyne cores remain obscure. Herein, we report pentaene polyols 5–7 and cinnamic acid derivatives 8 and 9 biosynthesized from an activated enediyne biosynthetic gene cluster in Streptomyces sp. CB02130. The C-1027 pksE could partially complement production of these polyene polyols in a CB02130 mutant where the native pksE is inactivated. The yields of 5–7 were improved by increasing the cellular pool of L-Phe through either gene inactivation of a prephenate dehydrogenase WlsPDH or supplementation of L-Phe. A flexible ammonia lyase WlsC4 is responsible for biosynthesis of 8 and 9 from L-Phe. The co-localization of wlsPDH and PKSE gene cassette supports their close evolutionary relationships and an enediyne genome mining strategy using WlsPDH. These findings not only provide a facile approach to activate silent enediyne BGCs, but suggest that a polyene epoxide intermediate may be formed for construction of 9-membered enediyne macrocycles.

Graphical abstract: Discovery of pentaene polyols by the activation of an enediyne gene cluster: biosynthetic implications for 9-membered enediyne core structures

Supplementary files

Article information

Article type
Edge Article
Submitted
05 Aug 2022
Accepted
28 Oct 2022
First published
31 Oct 2022
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., 2022,13, 13475-13481

Discovery of pentaene polyols by the activation of an enediyne gene cluster: biosynthetic implications for 9-membered enediyne core structures

J. Pan, Q. Tan, S. Zhu, X. Yan, Y. Li, Z. Zhuang, X. Zhu, Y. Duan and Y. Huang, Chem. Sci., 2022, 13, 13475 DOI: 10.1039/D2SC04379C

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