Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum
Abstract Background The production of androstenedione (AD) from phytosterols by Mycolicibacterium neoaurum is a multi-step biotransformation process, which requires degradation of sterol side chains, accompanied by the production of propionyl-CoA. However, the transient production of large amounts o...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-022-01942-x |
| _version_ | 1811336423572242432 |
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| author | Zhenhua Su Zhenjian Zhang Jian Yu Congcong Yuan Yanbing Shen Jianxin Wang Liqiu Su Min Wang |
| author_facet | Zhenhua Su Zhenjian Zhang Jian Yu Congcong Yuan Yanbing Shen Jianxin Wang Liqiu Su Min Wang |
| author_sort | Zhenhua Su |
| collection | DOAJ |
| description | Abstract Background The production of androstenedione (AD) from phytosterols by Mycolicibacterium neoaurum is a multi-step biotransformation process, which requires degradation of sterol side chains, accompanied by the production of propionyl-CoA. However, the transient production of large amounts of propionyl-CoA can accumulate intracellularly to produce toxic effects and severely inhibit AD production. Results In the present study, the intracellular propionyl-CoA concentration was effectively reduced and the productivity of the strain was improved by enhancing the cytosolic methyl-branched lipid synthesis pathway and increasing the expression level of nat operator gene, respectively. Subsequently, the application of a pathway combination strategy, combined and the inducible regulation strategy, further improved AD productivity with a maximum AD conversion rate of 96.88%, an increase of 13.93% over the original strain. Conclusions Overall, we provide a new strategy for reducing propionyl-CoA stress during biotransformation for the production of AD and other steroidal drugs using phytosterols. |
| first_indexed | 2024-04-13T17:39:16Z |
| format | Article |
| id | doaj.art-f4616366eb304bf7b9f49cc845339165 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-13T17:39:16Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-f4616366eb304bf7b9f49cc8453391652022-12-22T02:37:15ZengBMCMicrobial Cell Factories1475-28592022-10-0121111110.1186/s12934-022-01942-xCombined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurumZhenhua Su0Zhenjian Zhang1Jian Yu2Congcong Yuan3Yanbing Shen4Jianxin Wang5Liqiu Su6Min Wang7Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyFrontage Laboratories, IncKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyAbstract Background The production of androstenedione (AD) from phytosterols by Mycolicibacterium neoaurum is a multi-step biotransformation process, which requires degradation of sterol side chains, accompanied by the production of propionyl-CoA. However, the transient production of large amounts of propionyl-CoA can accumulate intracellularly to produce toxic effects and severely inhibit AD production. Results In the present study, the intracellular propionyl-CoA concentration was effectively reduced and the productivity of the strain was improved by enhancing the cytosolic methyl-branched lipid synthesis pathway and increasing the expression level of nat operator gene, respectively. Subsequently, the application of a pathway combination strategy, combined and the inducible regulation strategy, further improved AD productivity with a maximum AD conversion rate of 96.88%, an increase of 13.93% over the original strain. Conclusions Overall, we provide a new strategy for reducing propionyl-CoA stress during biotransformation for the production of AD and other steroidal drugs using phytosterols.https://doi.org/10.1186/s12934-022-01942-xMycolicibacterium neoaurumAndrostenonePropionyl-CoA metabolicPathway Associates |
| spellingShingle | Zhenhua Su Zhenjian Zhang Jian Yu Congcong Yuan Yanbing Shen Jianxin Wang Liqiu Su Min Wang Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum Microbial Cell Factories Mycolicibacterium neoaurum Androstenone Propionyl-CoA metabolic Pathway Associates |
| title | Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum |
| title_full | Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum |
| title_fullStr | Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum |
| title_full_unstemmed | Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum |
| title_short | Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum |
| title_sort | combined enhancement of the propionyl coa metabolic pathway for efficient androstenedione production in mycolicibacterium neoaurum |
| topic | Mycolicibacterium neoaurum Androstenone Propionyl-CoA metabolic Pathway Associates |
| url | https://doi.org/10.1186/s12934-022-01942-x |
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