抄録
The staurosporine biosynthetic gene cluster in Streptomyces sp. TP-A0274 consists of 15 sta genes. In the cluster, it was predicted that staN, which shows high similarity to cytochrome P450 is involved in C–N bond formation between the nitrogen at N-12 of aglycone and the carbon at C-5′ of deoxysugar. The staN disruptant produced holyrine A instead of staurosporine. The structure of holyrine A is aglycone linking to 2,3,6-trideoxy-3-aminoaldohexose between N-13 and C-1′ of deoxysugar. Holyrine A was converted to staurosporine by the staD disruptant. These results indicate that StaN, cytochrome P450 is responsible for C–N bond formation. This is the first example of C–N bond formation catalyzed by cytochrome P450. In addition, holyrine A was confirmed to be an intermediate of staurosporine biosynthesis, which suggests that the N- and O-methylation at C-3′ and C-4′ takes place after the formation of the C–N bond between C-5′ and N-12 in the biosynthetic pathway.
