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

Author:

Feng Jun12,Wu Jun1,Gao Jie1,Xia Zhigui2,Deng Zixin1,He Xinyi1

Affiliation:

1. State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

2. National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, Ministry of Health, and WHO Collaborating Centre for Malaria, Schistosomiasis and Filariasis, Shanghai, China

Abstract

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

Publisher

American Society for Microbiology

Subject

Ecology,Applied Microbiology and Biotechnology,Food Science,Biotechnology

Reference19 articles.

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3. Biosynthesis of blasticidin S from L-.alpha.-arginine. Stereochemistry in the arginine-2,3-aminomutase reaction

4. Studies on the biosynthesis of blasticidin S. Part I. Precursors of blasticidin S biosynthesis;Seto H;J. Antibiot. (Tokyo),1968

5. Biosynthesis of blasticidin S. Cell-free demonstration of n-methylation as the last step;Gould SJ;Bioorg. Med. Chem. Lett.,1991

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