Cytochrome P450 Homolog Is Responsible for C–N Bond Formation between Aglycone and Deoxysugar in the Staurosporine Biosynthesis of Streptomyces sp. TP-A0274
Cytochrome P450 Homolog Is Responsible for C–N Bond Formation between Aglycone and Deoxysugar in the Staurosporine Biosynthesis of Streptomyces sp. TP-A0274
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DOI：
10.1271/bbb.69.1753
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发表时间：
2005-01
期刊：
影响因子：
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通讯作者：
H. Onaka;Shumpei Asamizu;Y. Igarashi;R. Yoshida;T. Furumai
中科院分区：
文献类型：
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作者：
H. Onaka;Shumpei Asamizu;Y. Igarashi;R. Yoshida;T. Furumai
链霉菌中的星孢菌素生物合成基因簇。TP-A0274由15个sta基因组成。在该簇中，与细胞色素P450高度相似的Stan参与了苷元N-12位氮与脱氧糖C-5‘位碳之间C-N键的形成。斯坦干扰物产生的是冬凌碱A，而不是星形孢子素。冬凌草碱A的结构是在脱氧糖的N-13和C-1‘之间连接2，3，6-三脱氧-3-氨基醛已糖的苷元。霍利林A被STAD干扰物转化为星形孢子素。这些结果表明，Stan，细胞色素P450参与了C-N键的形成。这是细胞色素P450催化C-N键形成的第一个例子。此外，冬青碱A是星形孢菌素生物合成的中间体，这表明C-3‘和C-4’上的N-和O-甲基化发生在生物合成途径中C-5‘和N-12之间的C-N键形成之后。
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.