Efficient stereoselective hydroxylation of deoxycholic acid by the robust whole-cell cytochrome P450 CYP107D1 biocatalyst
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY(2023)
摘要
Deoxycholic acid (DCA) has been authorized by the Federal Drug Agency for cosmetic reduction of redundant submental fat. The hydroxylated product (613-OH DCA) was developed to improve the solubility and pharmaceutic properties of DCA for further applications. Herein, a combinatorial catalytic strategy was applied to construct a powerful Cytochrome P450 biocatalyst (CYP107D1, OleP) to convert DCA to 613-OH DCA. Firstly, the weak expression of OleP was significantly improved using pRSFDuet-1 plasmid in the E. coli C41 (DE3) strain. Next, the supply of heme was enhanced by the moderate overexpression of crucial genes in the heme biosynthetic pathway. In addition, a new biosensor was developed to select the appropriate redox partner. Furthermore, a cost-effective whole-cell catalytic system was constructed, resulting in the highest reported conversion rate of 613OH DCA (from 4.8% to 99.1%). The combinatorial catalytic strategies applied in this study provide an efficient method to synthesize high-value-added hydroxylated compounds by P450s.
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关键词
OleP,Deoxycholic acid,Hydroxylation,Redox partners,Whole-cell catalysis
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