Improving the production of 22-hydroxy-23,24-bisnorchol-4-ene-3-one in Mycolicibacterium smegmatis.
Journal
Microbial biotechnology
ISSN: 1751-7915
Titre abrégé: Microb Biotechnol
Pays: United States
ID NLM: 101316335
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
received:
06
06
2024
accepted:
29
07
2024
medline:
20
8
2024
pubmed:
20
8
2024
entrez:
19
8
2024
Statut:
ppublish
Résumé
The 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) is a C22 steroid synthon of pharmaceutical interest that can be produced as a lateral end-product of the catabolism of natural sterols (e.g., cholesterol or phytosterols). This work studies the role of an aldehyde dehydrogenase coded by the MSMEG_6563 gene of Mycolicibacterium smegmatis, named msRed, in 4-HBC production. This gene is located contiguously to the MSMEG_6561 encoding the aldolase msSal which catalyses the retroaldol elimination of acetyl-CoA of the metabolite intermediate 22-hydroxy-3-oxo-cholest-4-ene-24-carboxyl-CoA to deliver 3-oxo-4-pregnene-20-carboxyl aldehyde (3-OPA). We have demonstrated that msRed reduces 3-OPA to 4-HBC. Moreover, the role of msOpccR reductase encoded by MSMEG_1623 was also explored confirming that it also performs the reduction of 3-OPA into 4-HBC, but less efficiently than msRed. To obtain a M. smegmatis 4-HBC producer strain we deleted MSMEG_5903 (hsd4A) gene in strain MS6039-5941 (ΔkshB1, ΔkstD1) that produces 4-androstene-3,17-dione (AD) from natural sterols (cholesterol or phytosterols). The triple MS6039-5941-5903 mutant was able to produce 9 g/L of 4-HBC from 14 g/L of phytosterols in 2 L bioreactor, showing a productivity of 0.140 g/L h
Identifiants
pubmed: 39160452
doi: 10.1111/1751-7915.14551
doi:
Substances chimiques
Aldehyde Oxidoreductases
EC 1.2.-
Cholestenones
0
aldehyde dehydrogenase (NAD(P)+)
EC 1.2.1.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14551Subventions
Organisme : Ministerio de Economía y Competitividad
ID : PID2019-110612RB-I00
Organisme : Comunidad de Madrid
ID : S2018/BAA-4532
Informations de copyright
© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.
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