Biosynthesis of mevinolin, a hypocholesterolemic fungal metabolite, in Aspergillus terreus
Shiao, M.S.; Don, H.S.
Proceedings of the National Science Council Republic of China. Part B Life Sciences 11(3): 223-231
1987
ISSN/ISBN: 0255-6596 PMID: 3423140 Document Number: 302245
Mevinolin and compactin are fungal metabolites which inhibit cholesterol biosynthesis in mammalian systems. Biogenetically, mevinolin is formed from polyketide chains, one 18-carbon and one 4-carbon, derived from acetate in normal head to tail fashion. The remaining two carbons in mevinolin, namely C-2' and C-6 methyl groups, are transferred from S-adenosylmethionine. To distinguish the timing and sequence of these two methylation steps, [Me-14C] - and [Me-3H,14C]-L-methionine were fed to Aspergillus terreus at several selected production intervals. Location and distribution of labels were determined by the specific chemical degradation methods. The results have demonstrated clearly that transfer of methyl groups from two S-adenosylmethionine molecules to the biosynthetic precursors of mevinolin was a sequential process. Methylation at C-6 preceded that at C-2' of mevinolin. Both methylation steps proceeded with complete retention of hydrogens. Methyl groups were probably transferred to the anion-like intermediates.