Bile salt hydrolases: Structure and function, substrate preference, and inhibitor development
Open accessAbstract
The worldwide trend of limiting the use of antibiotic growth promoters (AGPs) in animal production creates challenges for the animal feed industry, thus necessitating the development of effective non‐antibiotic alternatives to improve animal performance. Increasing evidence has shown that the growth‐promoting effect of AGPs is highly correlated with the reduced activity of bile salt hydrolase (BSH, EC 3.5.1.24), an intestinal bacteria‐producing enzyme that has a negative impact on host fat digestion and energy harvest. Therefore, BSH inhibitors may become novel, attractive alternatives to AGPs. Detailed knowledge of BSH substrate preferences and the wealth of structural data on BSHs provide a solid foundation for rationally tailored BSH inhibitor design. This review focuses on the relationship between structure and function of BSHs based on the crystal structure, kinetic data, molecular docking and comparative structural analyses. The molecular basis for BSH substrate recognition is also discussed. Finally, recent advances and future prospectives in the development of potent, safe, and cost‐effective BSH inhibitors are described.
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N-terminal autocatalysis and oligomeric assembly in homotetramers are critical post-translational modifications to ensure active BSH enzymes.
“N-terminal autocatalysis and oligomeric assembly in homotetramers are critical post-translational modifications to ensure active BSH enzymes [87].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [87]
The Structural Basis for the Substrate Preference of BSHs section says autocatalytic processing activates the N-terminal catalytic Cys2. The Biochemical Properties and Substrate Preferences of BSHs section says most BSHs are homotetramers, but lists functional enzymes with other oligomeric forms; it does not establish homotetramer assembly as a necessary post-translational modification for activity. Page numbers were not provided for these passages. (LLM, conf=0.87)
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BileActome reveals community-assembled bile acid metabolism in the rumen microbiome
Zhang, B., Jiang, X., Zhao, H., & Wang, B. (2026) · ISME Communications · doi:10.1093/ismeco/ycag205
Du, Y., Qi, L., Shi, Y., Huang, X., Shi, X., Liu, M., Fang, Y., & Hu, X. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1912000
Wang, L., Li, J., Wang, H., Xue, X., Liu, S., & Yunzhi, Y. (2026) · Comparative Biochemistry and Physiology Part D Genomics and Proteomics · doi:10.1016/j.cbd.2026.102049
- Authors
- Dong, Z., & Lee, B. H.
- Affiliations
- Tianjin University of Science and Technology (CN)
- Kangwon National University (KR)
- Corresponding author
- Dong, Zixing
- Venue
- Protein Science
- Publisher
- Wiley
- Published
- 2018-09-24
- Volume
- 27
- Issue
- 10
- Pages
- 1742-1754
- ISSN
- 0961-8368 (ISSN-L)
- 1469-896X
- PMC
- PMC6199152
- OpenAlex
- W2887672362
- Cited by
- 92
- References
- 114
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 19 · 2023: 11 · 2022: 10 · 2021: 17 · 2020: 5 · 2019: 6
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Protein Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Youth Innovation Fund from Tianjin University of Science & Technology (2016LG15)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- bile salt hydrolase, antibiotic growth promoters, antibiotic alternatives, substrate recognition, substrate preference, enzyme structure-function, rational inhibitor design, crystal structure, enzyme kinetics, molecular docking, intestinal bacteria, feed additives
- MeSH terms
- Amidohydrolases, Animals, Enzyme Inhibitors, Humans, Molecular Structure
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