Biosynthesis of lactacystin.
The biosynthesis of lactacystin, a new microbial metabolite which induces differentiation of neuroblastoma cells, was studied by the feeding experiments of various 13C-labeled compounds and NMR spectroscopic analysis. The feeding experiments showed that lactacystin consists of three containing gamma-lactam moiety arises by a condensation between methylmalonic semialdehyde and C alpha position of L-leucine, followed by intramolecular cyclization. Two diastereotopic methyls, C-11 and C-12 of lactacystin were found to originate from the pro-R and pro-S methyls of leucine, respectively, as shown by incorporating a new type of chiral 13C-labeled L-leucine.
Takahashi
S
S
Department of Biosciences, Teikyo University, Utsunomiya, Japan.
Uchida
K
K
Nakagawa
A
A
Miyake
Y
Y
Kainosho
M
M
Matsuzaki
K
K
Omura
S
S
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism
D000900:Anti-Bacterial Agents; D015853:Cysteine Proteinase Inhibitors; C067713:lactacystin; D000111:Acetylcysteine