O- and N-methylation in the biosynthesis of staurosporine

The feeding of C-13- and H-2-enriched methionine to Streptomyces staurospor eus established that the methyl carbon and proton source of both the 3'-O- and 4'-N-methyl groups of staurosporine (1) was methionine and that all thr ee methyl protons from methionine were retained on 1. In the presence of th e methyltransferase inhibitor, sinefungin, the biosynthesis of staurosporin e was blocked at the last step, O-methylation. An intermediate, 3'-demethox y-3'-hydroxystaurosporine (2), was efficiently accumulated in the medium. O ther general methyltransferase inhibitors failed to produce any other staur osporine intermediates or analogues.