Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum.
Androstenone
Mycolicibacterium neoaurum
Pathway Associates
Propionyl-CoA metabolic
Journal
Microbial cell factories
ISSN: 1475-2859
Titre abrégé: Microb Cell Fact
Pays: England
ID NLM: 101139812
Informations de publication
Date de publication:
20 Oct 2022
20 Oct 2022
Historique:
received:
29
07
2022
accepted:
02
10
2022
entrez:
21
10
2022
pubmed:
22
10
2022
medline:
25
10
2022
Statut:
epublish
Résumé
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. 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. Overall, we provide a new strategy for reducing propionyl-CoA stress during biotransformation for the production of AD and other steroidal drugs using phytosterols.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 36266684
doi: 10.1186/s12934-022-01942-x
pii: 10.1186/s12934-022-01942-x
pmc: PMC9585753
doi:
Substances chimiques
Androstenedione
409J2J96VR
propionyl-coenzyme A
317-66-8
Phytosterols
0
Sterols
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
218Subventions
Organisme : National Natural Science Foundation of China
ID : 21978221
Organisme : Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project
ID : TSBICIP-KJGG-001-08
Organisme : National Key R&D Program of China, Synthetic Biology Research
ID : no. 2019YFA0905300
Organisme : Foundation (No. 2020KF003) of Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education and Tianjin Key Lab of Industrial Microbiology (Tianjin University of Science & Technology)
ID : No. 2020KF003
Informations de copyright
© 2022. The Author(s).
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