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Commun Biol. 2019 Apr 15;2:131. doi: 10.1038/s42003-019-0365-y. eCollection 2019.

Arsinothricin, an arsenic-containing non-proteinogenic amino acid analog of glutamate, is a broad-spectrum antibiotic.

Author information

1
1Department of Cellular Biology and Pharmacology, Florida International University, Herbert Wertheim College of Medicine, Miami, FL 33199 USA.
2
6Present Address: Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, 131 Princess Street, Manchester, M1 7DN UK.
3
2Planta Piloto de Procesos Industriales Microbiológicos (PROIMI-CONICET), Tucumán, T4001MVB Argentina.
4
3SER-CAT and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602 USA.
5
4Berkeley Center for Structural Biology, Lawrence Berkeley Laboratory, Berkeley, CA 94720 USA.
6
5Division of Hazardous Chemicals, National Institute for Agro-Environmental Sciences, NARO, Tsukuba, Ibaraki, 305-8604 Japan.
#
Contributed equally

Abstract

The emergence and spread of antimicrobial resistance highlights the urgent need for new antibiotics. Organoarsenicals have been used as antimicrobials since Paul Ehrlich's salvarsan. Recently a soil bacterium was shown to produce the organoarsenical arsinothricin. We demonstrate that arsinothricin, a non-proteinogenic analog of glutamate that inhibits glutamine synthetase, is an effective broad-spectrum antibiotic against both Gram-positive and Gram-negative bacteria, suggesting that bacteria have evolved the ability to utilize the pervasive environmental toxic metalloid arsenic to produce a potent antimicrobial. With every new antibiotic, resistance inevitably arises. The arsN1 gene, widely distributed in bacterial arsenic resistance (ars) operons, selectively confers resistance to arsinothricin by acetylation of the α-amino group. Crystal structures of ArsN1 N-acetyltransferase, with or without arsinothricin, shed light on the mechanism of its substrate selectivity. These findings have the potential for development of a new class of organoarsenical antimicrobials and ArsN1 inhibitors.

Conflict of interest statement

The authors have the following competing interest: Florida International University has applied for a US Non-Provisional patent application for “Arsinothricin and Methods of Treating Infections Using Arsinothricin” (US 16/163,055) with M.Y. and B.P.R. as inventors.

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