Production of Hydroxylated Steroid Intermediates at 10-g Scale via the Original Sterol Modification Pathway in Mycolicibacterium neoaurum

Zou, Lei; Li, Xue; Sun, Xue; Chang, Shangfeng; Chang, Zunxue

doi:10.3390/catal15050423

Open AccessArticle

Production of Hydroxylated Steroid Intermediates at 10-g Scale via the Original Sterol Modification Pathway in Mycolicibacterium neoaurum

by

Lei Zou

^1,2,

Xue Li

²,

Xue Sun

²,

Shangfeng Chang

^2,* and

Zunxue Chang

^1,2,*

¹

School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang 110016, China

²

Shenyang Botai Biopharmaceutial Ltd., Shenyang 110043, China

^*

Authors to whom correspondence should be addressed.

Catalysts 2025, 15(5), 423; https://doi.org/10.3390/catal15050423

Submission received: 25 March 2025 / Revised: 20 April 2025 / Accepted: 22 April 2025 / Published: 25 April 2025

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Abstract

The aerobic catabolism of steroids in bacteria is highly conserved, and the mechanism of steroid degradation in mycobacteria has been extensively studied. However, the branching modification pathways of steroids in mycobacteria remain a mystery, including the likely roles of cytochromes P450. In this study, we unraveled the CYP105S17 converting androst-4-ene-3,17-dione (AD) to 17β-hydroxy-4-androstene-3,16-dione (16-oxo-TS), which was subsequently reduced to 16α,17β-dihydroxy-androst-4-ene-3-one (16α-OH-TS) under reductive conditions in Mycolicibacterium neoaurum. By applying this modification pathway, the genetically modified strains overexpressing CYP105S17 were able to produce 16α-OH-TS at titers 13.0 g/L with a conversion rate of 91.9% (supplemented with 20 g/L phytosterols as the substrate) through a two-stage biotransformation process. This is the first instance of utilizing the native P450 of Mycobacterium to produce 16-hydroxylated steroid intermediates at the 10 g scale. This work provides invaluable perspectives and guidance to researchers seeking to understand the complexities of steroid metabolism in bacteria, and also highlights the great potential of Mycobacterium as a production platform for hydroxylated steroid intermediates or pharmaceuticals.

Keywords: Mycolicibacterium; 16-hydroxylation; steroid; CYP450

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MDPI and ACS Style

Zou, L.; Li, X.; Sun, X.; Chang, S.; Chang, Z. Production of Hydroxylated Steroid Intermediates at 10-g Scale via the Original Sterol Modification Pathway in Mycolicibacterium neoaurum. Catalysts 2025, 15, 423. https://doi.org/10.3390/catal15050423

AMA Style

Zou L, Li X, Sun X, Chang S, Chang Z. Production of Hydroxylated Steroid Intermediates at 10-g Scale via the Original Sterol Modification Pathway in Mycolicibacterium neoaurum. Catalysts. 2025; 15(5):423. https://doi.org/10.3390/catal15050423

Chicago/Turabian Style

Zou, Lei, Xue Li, Xue Sun, Shangfeng Chang, and Zunxue Chang. 2025. "Production of Hydroxylated Steroid Intermediates at 10-g Scale via the Original Sterol Modification Pathway in Mycolicibacterium neoaurum" Catalysts 15, no. 5: 423. https://doi.org/10.3390/catal15050423

APA Style

Zou, L., Li, X., Sun, X., Chang, S., & Chang, Z. (2025). Production of Hydroxylated Steroid Intermediates at 10-g Scale via the Original Sterol Modification Pathway in Mycolicibacterium neoaurum. Catalysts, 15(5), 423. https://doi.org/10.3390/catal15050423

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Production of Hydroxylated Steroid Intermediates at 10-g Scale via the Original Sterol Modification Pathway in Mycolicibacterium neoaurum

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