Issue 25, 2021
From the journal:

Chemical Science

An engineered biosynthetic–synthetic platform for production of halogenated indolmycin antibiotics†

Elesha R. Hoffarth, ORCID logo a   Sunnie Kong,a   Hai-Yan He‡a  and  Katherine S. Ryan ORCID logo *a  

* Corresponding authors

a Department of Chemistry, The University of British Columbia, Vancouver, Canada
E-mail: ksryan@chem.ubc.ca

Abstract

Indolmycin is an antibiotic from Streptomyces griseus ATCC 12648 with activity against Helicobacter pylori, Plasmodium falciparum, and methicillin-resistant Staphylococcus aureus. Here we describe the use of the indolmycin biosynthetic genes in E. coli to make indolmycenic acid, a chiral intermediate in indolmycin biosynthesis, which can then be converted to indolmycin through a three-step synthesis. To expand indolmycin structural diversity, we introduce a promiscuous tryptophanyl-tRNA synthetase gene (trpS) into our E. coli production system and feed halogenated indoles to generate the corresponding indolmycenic acids, ultimately allowing us to access indolmycin derivatives through synthesis. Bioactivity testing against methicillin-resistant Staphylococcus aureus showed modest antibiotic activity for 5-, 6-, and 7-fluoro-indolmycin.

Graphical abstract: An engineered biosynthetic–synthetic platform for production of halogenated indolmycin antibiotics

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DOI
https://doi.org/10.1039/D0SC05843B
Article type
Edge Article
Submitted
22 Oct 2020
Accepted
15 May 2021
First published
01 Jun 2021
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., 2021,12, 8817-8821

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An engineered biosynthetic–synthetic platform for production of halogenated indolmycin antibiotics

E. R. Hoffarth, S. Kong, H. He and K. S. Ryan, Chem. Sci., 2021, 12, 8817 DOI: 10.1039/D0SC05843B

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