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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

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


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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