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

Kexin Kong , Min Zhang , Hongmei Zhang , Chengyu Zhang , Chunhua Wang , Xiaohui Yan

Systems Microbiology and Biomanufacturing ›› 2022, Vol. 4 ›› Issue (1) : 1 -19.

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Systems Microbiology and Biomanufacturing ›› 2022, Vol. 4 ›› Issue (1) : 1 -19. DOI: 10.1007/s43393-022-00083-x
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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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Kexin Kong, Min Zhang, Hongmei Zhang, Chengyu Zhang, Chunhua Wang, Xiaohui Yan. Structures and molecular mechanisms of action of the cholesterol C17 side-chain-degrading enzymes. Systems Microbiology and Biomanufacturing, 2022, 4(1): 1-19 DOI:10.1007/s43393-022-00083-x

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National Key R&D Program of China, Synthetic Biology Research ,(2019YFA0905300)

Natural Science Foundation of China ,(81872779)

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