GenoChemetic Strategy for Derivatization of the Violacein Natural Product Scaffold

Overview

Journal ACS Chem Biol

Publisher American Chemical Society

Specialties Biochemistry
Biology

Date 2021 Oct 14

PMID 34648268

Citations 5

Authors

Hung-En Lai

Alan M C Obled

Soo Mei Chee

Rhodri M Morgan

Rosemary Lynch

Sunil V Sharma

Simon J Moore

Karen M Polizzi

Rebecca J M Goss

Paul S Freemont

Affiliations

Soon will be listed here.

Abstract

Natural products and their analogues are often challenging to synthesize due to their complex scaffolds and embedded functional groups. Solely relying on engineering the biosynthesis of natural products may lead to limited compound diversity. Integrating synthetic biology with synthetic chemistry allows rapid access to much more diverse portfolios of xenobiotic compounds, which may accelerate the discovery of new therapeutics. As a proof-of-concept, by supplementing an strain expressing the violacein biosynthesis pathway with 5-bromo-tryptophan or tryptophan 7-halogenase RebH , six halogenated analogues of violacein or deoxyviolacein were generated, demonstrating the promiscuity of the violacein biosynthesis pathway. Furthermore, 20 new derivatives were generated from 5-brominated violacein analogues via the Suzuki-Miyaura cross-coupling reaction directly using the crude extract without prior purification. Herein we demonstrate a flexible and rapid approach to access a diverse chemical space that can be applied to a wide range of natural product scaffolds.

Citing Articles

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Exploration of the In Vitro Violacein Synthetic Pathway with Substrate Analogues.

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