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Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum.
- Source :
-
Microbial Cell Factories . 10/20/2022, Vol. 21 Issue 1, p1-11. 11p. - Publication Year :
- 2022
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14752859
- Volume :
- 21
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Microbial Cell Factories
- Publication Type :
- Academic Journal
- Accession number :
- 159792282
- Full Text :
- https://doi.org/10.1186/s12934-022-01942-x