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

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.

Keywords

Steroid hormones / Cholesterol / Cholesterol C17 side-chain-degrading enzymes / β-Oxidation / Carbon–carbon bond cleavage / Cytochrome P450

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Funding

National Key R&D Program of China, Synthetic Biology Research(2019YFA0905300); Natural Science Foundation of China(81872779)