Chem Commun (Camb). 2026 Jul 12. doi: 10.1039/d6cc02702d. Online ahead of print.

ABSTRACT

Steroid synthesis is a cornerstone of pharmaceutical development, yet it remains hampered by the structural complexity of highly oxidized scaffolds and the presence of multiple stereogenic centers. Biocatalysis, characterized by unparalleled chemo-, regio-, and stereoselectivity, provides a sustainable and high-precision alternative for steroid manufacturing. This review focuses on sterol side-chain modification and the precise hydroxylation of the steroid nucleus, integrating our group’s research to systematically summarize recent advancements in steroid synthesis. Key areas covered include: (i) the mining and characterization of key enzymes involved in sterol side-chain degradation, (ii) the discovery and application of P450scc in the de novo synthesis of steroid intermediates, (iii) the identification of rare-site steroid hydroxylases for the efficient production of highly oxidized steroids, (iv) the engineering of P450 peroxygenase activity, and (v) the elucidation of biosynthetic pathways for the C17 side chain of high-value steroid natural products. Overall, this review aims to provide theoretical insights that can guide the development of more efficient steroid synthesis strategies.

PMID:42437391 | DOI:10.1039/d6cc02702d