BIOSYNTHESIS OF PYRIPYROPENE-A

The biosynthetic origin of pyripyropene A ii) was studied by feeding s odium [1-C-13]-, [2-C-13]-, and [1,2-C-13(2)]acetates, D,L-[2-C-13]mev alonolactone, and [carboxy-C-14]nicotinic acid to the producing organi sm Aspergillus fumigatus FO-1289-2501. C-13 NMR and degradation experi ments of C-13- and C-14-labeled 1 established that 1 is derived from t hree mevalonates, five acetates, and one nicotinic acid. The biosynthe tic scheme for 1 proposes that !1) a pyridino-alpha-pyrone moiety is p roduced via condensation of a primer nicotinic acid with two acetates in a ''head-to-tail'' fashion, (2) an all-trans farnesyl pyrophosphate is produced via the mevalonate pathway, (3) the two parts are linked and cyclized to form the core skeleton, and (4) then three acetyl resi dues from acetates are introduced into the skeleton to yield 1. This i s the first demonstration that an intact nicotinic acid works as an ac yl primer unit for oligoketide formation in fungal secondary metabolit es.