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  • 标题:Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus
  • 本地全文:下载
  • 作者:QIANQIAN LI ; LI SHI ; YINGYING LIU
  • 期刊名称:Acta Pharmaceutica
  • 电子版ISSN:1846-9558
  • 出版年度:2021
  • 卷号:71
  • 期号:1
  • DOI:10.2478/acph-2021-0004
  • 语种:English
  • 出版社:Sciendo
  • 摘要: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 potential for application in the industrial production of eplerenone.
  • 关键词:Aspergillus ochraceus;P450 monooxygenase;homologous recombination;canrenone;11α-hydroxycanrenone
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