| 标题 |
  Exploring PTDH-P450BM3 Variants for the Synthesis of Drug Metabolites 相关领域
芳构化
羟基化
化学
去甲基化
辅因子
酶
细胞色素P450
基质（水族馆）
加氧酶
生物化学
细胞色素
立体化学
组合化学
催化作用
生物
基因
基因表达
生态学
DNA甲基化
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| 网址 | |
| DOI | |
| 其它 | The conversion of a series of pharmaceutical compounds was examined with three variants of cytochrome P450BM3 fused to phosphite dehydrogenase (PTDH) to enable cofactor recycling. Conditions for enzyme production were optimized, and the purified PTDH-P450BM3 variants were tested against 32 commercial drugs by using rapid UPLC-MS analysis. The sets of mutations (R47L/F87V/L188Q and R47L/F87V/L188Q/E267V/G415S) improved conversion for all compounds, and a variety of products were detected. Product analysis showed that reaction types included C-hydroxylation, N-oxidation, demethylation, and aromatization. Interestingly, enzymatic aromatization could occur independent of the addition of reducing coenzyme. These results identified new conversions catalyzed by P450BM3 variants and showed that a small set of mutations in the oxygenase domain could broaden both substrate range and reaction type. |
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