Cytochrome P450 homolog is responsible for C-N bond formation between aglycone and deoxysugar in the staurosporine biosynthesis of Streptomyces sp. TP-A0274

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2005-09, Vol.69 (9), p.1753-1759
• Main Authors: Onaka, H.(Toyama Prefectural Univ., Kosugi (Japan). Faculty of Engineering), Asamizu, S, Igarashi, Y, Yoshida, R, Furumai, T
• Format: Article
• Language: English
• Subjects: Amines - chemistry; Amino Acid Sequence; BIOCHEMICAL PATHWAYS; Biological and medical sciences; BIOSINTESIS; BIOSYNTHESE; BIOSYNTHESIS; Carbazoles; CHEMICAL STRUCTURE; CITOCROMO P450; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; CYTOCHROME P450; Deoxy Sugars - chemistry; Deoxy Sugars - metabolism; Doxorubicin - analogs & derivatives; Doxorubicin - chemistry; Doxorubicin - metabolism; ESTRUCTURA QUIMICA; Fundamental and applied biological sciences. Psychology; GLICOSIDOS; GLYCOSIDE; GLYCOSIDES; Indoles; indolocarbazole; Models, Chemical; Models, Theoretical; Molecular Sequence Data; Mutation; Sequence Homology, Amino Acid; staurosporine; Staurosporine - biosynthesis; STREPTOMYCES; Streptomyces - enzymology; Streptomyces - genetics; Streptomyces - metabolism; STRUCTURE CHIMIQUE; VIA BIOQUIMICA DEL METABOLISMO; VOIE BIOCHIMIQUE DU METABOLISME
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.69.1753

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.