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Structures and molecular mechanisms of action of the cholesterol C17 side-chain-degrading enzymes

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Abstract

Cholesterol, an essential lipid for mammalian cells, can be used as a carbon source by bacteria and as a precursor for steroid hormones in animal cells. The cholesterol C17 side-chain-cleavage pathways are the committed and rate-limiting steps in the biosynthesis of steroid drugs. Three cholesterol C17 side-chain degradation pathways have been identified in nature: the β-oxidation pathways in actinobacteria, the oxygen-independent degradation pathway in Sterolibacterium denitrificans, and the cholesterol side-chain degradation pathway in mammals. An in-depth understanding of the structures and molecular mechanisms of enzymes in these degradation processes will facilitate the creation of enzyme mutants with better catalytic capabilities. The introduction of the engineered enzymes into the microbial cell factories may contribute to the industrial production of steroid drugs.

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Funding

This work was financially supported by the National Key Research and Development Program of China (2019YFA0905300) and the Natural Science Foundation of China (no. 81872779).

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  1. Kexin Kong and Min Zhang contribute equally to this manuscript.

Authors and Affiliations

  1. State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, China

    Kexin Kong, Min Zhang, Chengyu Zhang & Xiaohui Yan

  2. Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Hongmei Zhang & Chunhua Wang

  3. College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, China

    Hongmei Zhang & Chunhua Wang

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  1. Kexin Kong
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  2. Min Zhang
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  3. Hongmei Zhang
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  4. Chengyu Zhang
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Correspondence to Chunhua Wang or Xiaohui Yan.

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Kong, K., Zhang, M., Zhang, H. et al. Structures and molecular mechanisms of action of the cholesterol C17 side-chain-degrading enzymes. Syst Microbiol and Biomanuf 4, 1–19 (2024). https://doi.org/10.1007/s43393-022-00083-x

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