Autor: |
Chixiang Sun, Baodong Hu, Yanchun Li, Zhimeng Wu, Jingwen Zhou, Jianghua Li, Jian Chen, Guocheng Du, Xinrui Zhao |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
|
Zdroj: |
Synthetic and Systems Biotechnology, Vol 8, Iss 4, Pp 741-748 (2023) |
Druh dokumentu: |
article |
ISSN: |
2405-805X |
DOI: |
10.1016/j.synbio.2023.11.008 |
Popis: |
Deoxycholic acid (DCA) has been authorized by the Federal Drug Agency for cosmetic reduction of redundant submental fat. The hydroxylated product (6β-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 6β-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 6β-OH 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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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