Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus
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, i...
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2021-03-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2021-0004 |
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| author | Li Qianqian Shi Li Liu Yingying Guan Shimin Zhang Shuo Cai Baoguo Rong Shaofeng |
| author_facet | Li Qianqian Shi Li Liu Yingying Guan Shimin Zhang Shuo Cai Baoguo Rong Shaofeng |
| author_sort | Li Qianqian |
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| description | 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. |
| format | Article |
| id | doaj-art-9cd68267b658415192841c8e16a5f22d |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-9cd68267b658415192841c8e16a5f22d2025-02-02T00:31:54ZengSciendoActa Pharmaceutica1846-95582021-03-017119911410.2478/acph-2021-0004acph-2021-0004Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceusLi Qianqian0Shi Li1Liu Yingying2Guan Shimin3Zhang Shuo4Cai Baoguo5Rong Shaofeng6Department of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, ChinaDepartment of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, ChinaDepartment of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, ChinaDepartment of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, ChinaDepartment of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, ChinaDepartment of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, ChinaDepartment of Bioengineering Shanghai Institute of TechnologyFengxian, Shanghai, 201418, ChinaEplerenone 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.https://doi.org/10.2478/acph-2021-0004aspergillus ochraceusp450 monooxygenasehomo-logous recombinationcanrenone11α-hydroxycanrenone |
| spellingShingle | Li Qianqian Shi Li Liu Yingying Guan Shimin Zhang Shuo Cai Baoguo Rong Shaofeng Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus Acta Pharmaceutica aspergillus ochraceus p450 monooxygenase homo-logous recombination canrenone 11α-hydroxycanrenone |
| title | Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus |
| title_full | Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus |
| title_fullStr | Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus |
| title_full_unstemmed | Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus |
| title_short | Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus |
| title_sort | improved 11α hydroxycanrenone production by modification of cytochrome p450 monooxygenase gene in aspergillus ochraceus |
| topic | aspergillus ochraceus p450 monooxygenase homo-logous recombination canrenone 11α-hydroxycanrenone |
| url | https://doi.org/10.2478/acph-2021-0004 |
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