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Issue 2, 2021
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Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases

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Abstract

For most antimicrobial compounds with intracellular targets, getting inside the cell is the major obstacle limiting their activity. To pass this barrier some antibiotics mimic the compounds of specific interest for the microbe (siderophores, peptides, carbohydrates, etc.) and hijack the transport systems involved in their active uptake followed by the release of a toxic warhead inside the cell. In this review, we summarize the information about the structures, biosynthesis, and transport of natural inhibitors of aminoacyl-tRNA synthetases (albomycin, microcin C-related compounds, and agrocin 84) that rely on such “Trojan horse” strategy to enter the cell. In addition, we provide new data on the composition and distribution of biosynthetic gene clusters reminiscent of those coding for known Trojan horse aminoacyl-tRNA synthetases inhibitors. The products of these clusters are likely new antimicrobials that warrant further investigation.

Graphical abstract: Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases

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Supplementary files

Article information


Submitted
16 Nov 2020
Accepted
10 Feb 2021
First published
22 Feb 2021

This article is Open Access

RSC Chem. Biol., 2021,2, 468-485
Article type
Review Article

Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases

D. Y. Travin, K. Severinov and S. Dubiley, RSC Chem. Biol., 2021, 2, 468
DOI: 10.1039/D0CB00208A

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