O- and N-methylation in the biosynthesis of staurosporine.
The feeding of (13)C- and (2)H-enriched methionine to Streptomyces staurosporeus 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 three methyl protons from methionine were retained on 1. In the presence of the methyltransferase inhibitor, sinefungin, the biosynthesis of staurosporine was blocked at the last step, O-methylation. An intermediate, 3'-demethoxy-3'-hydroxystaurosporine (2), was efficiently accumulated in the medium. Other general methyltransferase inhibitors failed to produce any other staurosporine intermediates or analogues.
Yang
S W
SW
Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Lin
L J
LJ
Cordell
G A
GA
Wang
P
P
Corley
D G
DG
D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D013056:Spectrophotometry, Ultraviolet; D019311:Staurosporine / Q000096:biosynthesis*; D013302:Streptomyces / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008780:Methyltransferases; D019311:Staurosporine