Biosynthesis of the β-Methylarginine Residue of Peptidyl Nucleoside Arginomycin in Streptomyces arginensis NRRL 15941

• DOI: 10.1128/aem.01172-14
• Publication Date: 2014-06-07T08:26:22Z
• Authors: Jun Feng; Jun Wu; Jie Gao; Zhigui Xia; Zixin Deng; Xinyi He
• Keywords: Transamination

The peptidyl nucleoside arginomycin is active against Gram-positive bacteria and fungi but displays much lower toxicity to mice than its analog blasticidin S. It features a rare amino acid, β-methylarginine, which attached the deoxyhexose moiety via 4'-aminoacyl bond. We here report cloning of complete biosynthetic gene cluster for from Streptomyces arginensis NRRL 15941. Among 14 putative essential open reading frames, argM, encoding an aspartate aminotransferase (AAT), adjacent argN, S-adenosyl methionine (SAM)-dependent methyltransferase, are coupled catalyze arginine yield β-methylarginine in Escherichia coli. Purified ArgM can transfer α-amino group l-arginine α-ketoglutaric acid give glutamate thereby converts 5-guanidino-2-oxopentanoic methylated at C-3 position by ArgN form 5-guanidino-3-methyl-2-oxopentanoic acid. Iteratively, specifically catalyzes transamination donor l-aspartate resulting generating β-methylarginine. concise pathway bioactive revealed this study may pave way production either enzymatic conversion or engineered living cells.