Nonenzymatic Oxidative Steps Accompanying Action of the Cytochrome P450 Enzymes StaP and RebP in the Biosynthesis of Staurosporine and Rebeccamycin

摘要

Biosynthesis of the antitumor indolocarbazoles rebeccamycin and staurosporine involves a complex series of oxidative coupling reactions,catalyzed by heme and flavin-based enzymes,starting from the common amino acid L-tryptophan.Most intriguing among these is the four-to eight-electron oxidation of chromopy-rrolic acid(CPA)1 to the three aglycones,K252c 3,7-hydroxy-K252c 4,and arcyriaflavin A 5,which can be catalyzed by the single cytochrome P450 enzyme,StaP(or its homologue from the rebeccamycin pathway,RebP)(Scheme 1).