ABSTRACT
Antimicrobial resistance is an emerging global public health crisis, calling for urgent development of novel potent antibiotics. We recently demonstrated that arsinothricin (AST), the novel organoarsenical produced from arsenite (As(III)) by a soil bacterium, is effective against both Gram-positive and Gram-negative bacteria, suggesting that microbes utilize environmental arsenic to synthesize potent broad-spectrum antimicrobials for dominance in the community. AST is effective against resistant pathogens, demonstrating the potential to address the global threat of drug resistance. Here we report identification of the biosynthetic gene cluster (BGC) of AST from the producer, Burkholderia gladioli GSRB05. We sequenced the B. gladioli genome and found a seven-gene BGC containing arsM for As(III) S-adenosylmethionine (SAM) methyltransferase. Heterologous expression of the BGC confers AST production in Escherichia coli. Mutagenesis analysis suggests that only two genes, arsM and an adjacent gene encoding a radical SAM protein, termed arsL, are required for AST biosynthesis. The role of the additional genes is under investigation. Our results demonstrate that the biosynthetic pathway of AST is relatively straightforward.
