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Enhancing production and purity of 9-OH-AD from phytosterols by balancing metabolic flux of the side-chain degradation and 9-position hydroxylation in Mycobacterium neoaurum.
- Source :
-
Biotechnology journal [Biotechnol J] 2024 Jan; Vol. 19 (1), pp. e2300439. Date of Electronic Publication: 2023 Dec 21. - Publication Year :
- 2024
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Abstract
- 9α-Hydroxyandroster-4-ene-3,17-dione (9-OH-AD) is a representative steroid drug intermediate that can be prepared by phytosterols (PS) biotransformation with mycobacteria in a resting cell-cyclodextrin system. In this study, over-expression of 17β-hydroxysteroid dehydrogenase (Hsd4A) was testified to enhance the side-chain degradation of PS and to reduce the incomplete degradation by-products. Meanwhile, the complete degradation product 4-androstene-3,17-dione (AD) was increased due to the lack of 3-Ketosteroid 9α-Hydroxylase (KshA1) activities. To increase the production and purity of 9-OH-AD, the metabolic pathway of the side-chain degradation of PS and 9-position hydroxylation was modulated by balancing the over-expression of Hsd4A and KshA1 in mycobacteria and reducing the bioconversion rate via lowering the ratio of PS and cyclodextrin. The production and purity of 9-OH-AD in broth were improved from 22.18 g L <superscript>-1</superscript> and 77.13% to 28.27 g L <superscript>-1</superscript> and 87.84%, with a molar yield of 78.32%.<br /> (© 2023 Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 1860-7314
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biotechnology journal
- Publication Type :
- Academic Journal
- Accession number :
- 38129322
- Full Text :
- https://doi.org/10.1002/biot.202300439