Semisynthesis of the Organoarsenical Antibiotic Arsinothricin
Sazzad H. Suzol, A. Hasan Howlader, Adriana E. Galván, Manohar Radhakrishnan, Stanislaw F. Wnuk, Barry P. Rosen, Masahiro Yoshinaga
Abstract
Arsinothricin [AST (1)], a new broad-spectrum organoarsenical antibiotic, is a nonproteinogenic analogue of glutamate that effectively inhibits glutamine synthetase. We report the chemical synthesis of an intermediate in the pathway to 1, hydroxyarsinothricin [AST-OH (2)], which can be converted to 1 by enzymatic methylation catalyzed by the ArsM As(III) S-adenosylmethionine methyltransferase. This is the first report of semisynthesis of 1, providing a source of this novel antibiotic that will be required for future clinical trials.
Topics & Concepts
SemisynthesisGlutamine synthetaseAntibioticsMethylationStereochemistryMethyltransferaseGlutamineChemistryBiochemistryEnzymeCombinatorial chemistryAmino acidDNABiochemical and Molecular ResearchCancer therapeutics and mechanismsMicrobial Natural Products and Biosynthesis