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Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus

Authors :
Li Qianqian
Shi Li
Liu Yingying
Guan Shimin
Zhang Shuo
Cai Baoguo
Rong Shaofeng
Source :
Acta Pharmaceutica, Vol 71, Iss 1, Pp 99-114 (2021)
Publication Year :
2021
Publisher :
Sciendo, 2021.

Abstract

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.

Details

Language :
English
ISSN :
18469558
Volume :
71
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Acta Pharmaceutica
Publication Type :
Academic Journal
Accession number :
edsdoj.9cd68267b658415192841c8e16a5f22d
Document Type :
article
Full Text :
https://doi.org/10.2478/acph-2021-0004