title: Biosynthesis of the β-methylarginine residue of peptidyl nucleoside arginomycin in Streptomyces arginensis NRRL 15941.
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.
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Zhigui
authors.initials: Z
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China xyhe@sjtu.edu.cn.
authors.forename: Xinyi
authors.initials: X
authors.lastname: He
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis* / Q000737:chemistry; D001120:Arginine / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D001426:Bacterial Proteins; C053076:arginomycin; D001120:Arginine; D008780:Methyltransferases; D001219:Aspartate Aminotransferases