Biosynthesis of Lactacystin

抄録

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 biosynthetic units, namely isobutyrate (and/or L-valine), L-leucine and L-cysteine. The C₁₀ unit containing γ-lactam moiety arises by a condensation between methylmalonic semialdehyde and C_α 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.