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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
  • +1
  • xiaomei zhu,
  • Xiao Wang,
  • Jian Zhang,
  • Xuedong wang
xiaomei zhu
East China University of Science and Technology State Key Laboratory of Bioreactor Engineering
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Xiao Wang
East China University of Science and Technology State Key Laboratory of Bioreactor Engineering
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Jian Zhang
East China University of Science and Technology State Key Laboratory of Bioreactor Engineering
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Xuedong wang
East China University of Science and Technology State Key Laboratory of Bioreactor Engineering

Corresponding Author:[email protected]

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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 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 and 77.13% to 28.27 g/L and 87.84%, with a molar yield of 78.32%.
27 Aug 2023Submitted to Biotechnology Journal
27 Aug 2023Submission Checks Completed
27 Aug 2023Assigned to Editor
01 Sep 2023Reviewer(s) Assigned
11 Nov 2023Review(s) Completed, Editorial Evaluation Pending
13 Nov 2023Editorial Decision: Revise Minor