Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus.
Autor: | Li Q; Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, China., Shi L; Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, China., Liu Y; Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, China., Guan S; Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, China., Zhang S; Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, China., Cai B; Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, China., Rong S; Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, China. |
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Jazyk: | angličtina |
Zdroj: | Acta pharmaceutica (Zagreb, Croatia) [Acta Pharm] 2021 Mar 01; Vol. 71 (1), pp. 99-114. |
DOI: | 10.2478/acph-2021-0004 |
Abstrakt: | Eplerenone is a drug that protects the cardiovascular system. 11α-Hydroxycanrenone is a key intermediate in eplerenone synthesis. We found that although the cytochrome P450 (CYP) enzyme system in Aspergillus ochraceus strain MF018 could catalyse the conversion of canrenone to 11α-hydroxycanrenone, its biocatalytic efficiency is low. To improve the efficiency of 11α-hydroxycanrenone production, the CYP monooxygenase-coding gene of MF018 was predicted and cloned based on whole-genome sequencing results. A recombinant A. ochraceus strain MF010 with the high expression of CYP monooxygenase was then obtained through homologous recombination. The biocatalytic rate of this recombinant strain reached 93 % at 60 h without the addition of organic solvents or surfactants and was 17-18 % higher than that of the MF018 strain. Moreover, the biocatalytic time of the MF010 strain was reduced by more than 30 h compared with that of the MF018 strain. These results show that the recombinant A. ochraceus strain MF010 can overcome the limitation of substrate biocatalytic efficiency and thus holds a high poten tial for application in the industrial production of eplerenone. |
Databáze: | MEDLINE |
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