Divergent Conversion Efficiencies of Mycobacterium sp. 191574 for Various Phytosterols and Their Underlying Mechanisms

TL;DR

This study explores how efficiently a type of bacteria can convert different plant sterols into steroid drug ingredients and identifies the reasons behind the differences.

Contribution

The study reveals the conversion efficiency differences and identifies key enzymes affecting stigmasterol conversion in Mycobacterium sp. 191574.

Findings

β-sitosterol showed the highest conversion efficiency, while stigmasterol had the lowest.

Proteomic analysis identified acyl-CoA synthetase and hydrolase as rate-limiting enzymes for stigmasterol conversion.

Molecular docking showed reduced binding affinity of stigmasterol due to structural differences.

Abstract

Steroid drugs have a broad range of applications in medicine. The microbial degradation of phytosterols for the synthesis of steroid drug intermediates holds significant potential for industrial applications. In this study, the transformation efficiency and underlying mechanisms of different phytosterols in Mycobacterium sp. 191574 were investigated. Among the tested compounds, β-sitosterol exhibited the highest conversion efficiency, followed by mixed sterols, while stigmasterol showed the lowest efficiency. Proteomic analysis identified key enzymes involved in sterol metabolism. Further molecular docking experiments revealed that acyl-CoA synthetase (A0A0T1W1C0) and hydrolase (A0A0T1W815) may act as rate-limiting enzymes contributing to the low conversion rate of stigmasterol. Significant differences in hydrogen bonding patterns and three-dimensional spatial structures between these enzymes and sterol-derived ligands were observed, resulting in reduced binding affinity of stigmasterol. This study provides a theoretical basis for the optimization of sterol biotransformation processes and offers a foundation for improving the biological production efficiency of sterol-based pharmaceutical intermediates.

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