Open AccessCytochrome P450 Homolog Is Responsible for C–N Bond Formation between Aglycone and Deoxysugar in the Staurosporine Biosynthesis ofStreptomycessp. TP-A0274
Author(s) -
Hiroyasu Onaka,
Shumpei Asamizu,
Yasuhiro Igarashi,
Ryuji Yoshida,
Tamotsu Furumai
Publication year - 2005
Publication title -
bioscience, biotechnology, and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.509
H-Index - 116
eISSN - 1347-6947
pISSN - 0916-8451
DOI - 10.1271/bbb.69.1753
Subject(s) - aglycone , staurosporine , cytochrome p450 , biosynthesis , gene cluster , cytochrome c , stereochemistry , chemistry , biochemistry , enzyme , gene , apoptosis , protein kinase c , glycoside
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.