Cytochrome P450 homolog is responsible for C-N bond formation between aglycone and deoxysugar in the staurosporine biosynthesis of Streptomyces sp. TP-A0274.
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.
Onaka
Hiroyasu
H
Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan. onaka@pu-toyama.ac.jp
Asamizu
Shumpei
S
Igarashi
Yasuhiro
Y
Yoshida
Ryuji
R
Furumai
Tamotsu
T
D000588:Amines / Q000737:chemistry*; D000595:Amino Acid Sequence; D002227:Carbazoles; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003837:Deoxy Sugars / Q000737:chemistry / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D007211:Indoles; D008956:Models, Chemical; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D019311:Staurosporine / Q000096:biosynthesis*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D000588:Amines; D002227:Carbazoles; D003837:Deoxy Sugars; D007211:Indoles; C074869:7-deoxy-13-dihydroadriamycinone; D004317:Doxorubicin; D003577:Cytochrome P-450 Enzyme System; C053339:rebeccamycin; D019311:Staurosporine