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

Article abstract of DOI:10.1021/ja00225a033

A series of labeled α-arginines have been fed to fermentations of Streptomyces griseochromogenes in order to examine the mechanism of L-β-arginine formation in the biosynthesis of the antibiotic blasticidin S. [3-¹³C,2-¹⁵N]Arginine was synthesized and fed; analysis of the derived antibiotic by ¹³C NMR spectroscopy revealed the retention of the original α-nitrogen and its intramolecular migration to the β-position, revealing the presence of an arginine-2,3-aminomutase. Feedings of [2,3,3-²H₃]-, [3,3-²H₂]-, and [2-²H]arginines revealed the complete retention of the original β-hydrogens with migration of one to the α-position, as well as partial loss of the original α-hydrogen presumably due to arginine racemase activity. (3R)-[3-²H]- and (3S)-[3-²H]arginines were synthesized unambiguously and used to determine that the pro-3R hydrogen of α-arginine migrates to the α-position (C-2). δ-N-[¹³CH₃]Methylarginine was synthesized, mixed with [guanidino-¹⁴C]arginine, and fed to S. griseochromogenes. A 42% incorporation of radioactivity from arginine was obtained, but no ¹³C enrichment was observed in the blasticidin S sample, indicating that arginine, itself, is the aminomutase substrate.