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Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum.
- Source :
-
Microbial cell factories [Microb Cell Fact] 2022 Oct 20; Vol. 21 (1), pp. 218. Date of Electronic Publication: 2022 Oct 20. - 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.<br />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.<br />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.<br /> (© 2022. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1475-2859
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Microbial cell factories
- Publication Type :
- Academic Journal
- Accession number :
- 36266684
- Full Text :
- https://doi.org/10.1186/s12934-022-01942-x