Improving the bioconversion of phytosterols to 9α-hydroxy-4-androstene-3,17-dione by disruption of acyltransferase SucT and TmaT associated with the mycobacterial cell wall synthesis.
9α-hydroxyandrost-4-ene-3,17-dione
Acyltransferases SucT and TmaT
Cell wall engineering
Lipoarabinomannan acylation
Trehalose mycolates transport
Journal
World journal of microbiology & biotechnology
ISSN: 1573-0972
Titre abrégé: World J Microbiol Biotechnol
Pays: Germany
ID NLM: 9012472
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
received:
08
08
2024
accepted:
09
10
2024
medline:
15
10
2024
pubmed:
15
10
2024
entrez:
15
10
2024
Statut:
epublish
Résumé
The bioconversion of low value-added phytosterols into high value-added 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) in Mycolicibacterium neoaurum is a representative step in the steroid pharmaceutical industry. However, the complex mycobacterial cell walls with extremely low permeability and flowability greatly decrease the overall conversion efficiency. Herein, we preliminarily identified two key acyltransferases encoded by Mn_TmaT and Mn_SucT required for the proper synthesis of cell wall in mycobacteria and achieved a significant increase in cell permeability by disrupting them without affecting the cell wall structural stability. At length, the destruction of Mn_TmaT and Mn_SucT alone increased the conversion rate of 9-OHAD from 45.3% (6.67 ± 0.39 g/L) to 62.4% (9.19 ± 0.58 g/L) and 67.9% (10.02 ± 0.62 g/L) while the continuous destruction of Mn_TmaT and Mn_SucT did not further improve the conversion efficiency of 9-OHAD. Notably, it was investigated that the continuous destruction of Mn_TmaT and Mn_SucT led to alterations in both the covalent and non-covalent binding layers of the cell wall, resulting in excessive changes in cell morphology and structure, which ultimately decreased 9-OHAD production. Therefore, this study deciphered a pivotal biosynthetic path of cell wall and provided an efficient and feasible construction strategy of 9-OHAD synthesis in mycobacteria.
Identifiants
pubmed: 39404941
doi: 10.1007/s11274-024-04165-x
pii: 10.1007/s11274-024-04165-x
doi:
Substances chimiques
Phytosterols
0
Androstenedione
409J2J96VR
9-hydroxy-4-androstene-3,17-dione
560-62-3
Acyltransferases
EC 2.3.-
Bacterial Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
350Subventions
Organisme : National Key Research and Development Program of China
ID : 2019YFA0905300
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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