Studies on novel bacterial translocase I inhibitors, A-500359s. IV. Biosynthesis of A-500359s.
This report describes the isolation of novel A-500359 analogues from the culture broth of Streptomyces griseus SANK 60196 and 13C-incorporation studies of A-500359 A to reveal the biosynthetic pathway of A-500359 derivatives. As a result, A-500359 M-3 and J were isolated as novel analogues. The former, isolated from a culture broth fed with unnatural amino acids, was a novel amino acid adduct of A-500359, and the latter was found to be a putative precursor of all A-500359 derivatives, on the basis of the structure. Moreover, 13C-incorporation studies revealed the origin of every carbon atom of A-500359 A. From these results, it was revealed that the core skeleton of A-500359 was biosynthesized from uridine and phosphoenolpyruvate in the same manner as for polyoxin, a nucleoside antibiotic. Moreover, the uronic acid and aminocaprolactam moiety was derived from hexose and lysine, respectively, and two methyl groups of A-500359 A were derived from methionine.
Ohnuki
Takashi
T
Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., 1-2-58, Hiromachi Shinagawa-ku, Tokyo 140-8710, Japan.
Muramatsu
Yasunori
Y
Miyakoshi
Shunichi
S
Takatsu
Toshio
T
Inukai
Masatoshi
M
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005285:Fermentation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors*; D014529:Uridine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001381:Azepines; D004791:Enzyme Inhibitors; C049983:capuramycin; D017855:Transferases (Other Substituted Phosphate Groups); C100130:phospho-N-acetylmuramoyl pentapeptide transferase; D014529:Uridine