[Research advances in CYP450-mediated biosynthetic pathways of steroids in plants]

Steroids, a group of diverse plant-derived natural products, exhibit not only essential physiological roles but also significant pharmacological activities, including anti-tumor, anti-viral, antibacterial, anti-inflammatory, blood glucose- and lipid-lowering, hepatoprotective, and immunomodulatory properties. The cytochrome P450 monooxygenase (CYP450) superfamily constitutes a class of heme-containing enzymes capable of catalyzing remarkably regiospecific and stereospecific oxidative reactions. CYP450s serve as pivotal catalysts for structural modifications of steroids in plants. This review comprehensively summarizes the functionally characterized CYP450 proteins that participate in plant steroid biosynthesis, which encompasses backbone formation (C-14 demethylation and side chain degradation) and structural modifications of both steroid skeleton and side chains. Focusing on distinct structural features of steroid skeletons and side chains, we highlight recent advances in CYP450-mediated biosynthetic pathways of Δ²²-sterols, brassinosteroids, cholesterol derivatives, and withanolides, with a particular emphasis on the impacts of oxidative modifications on the bioactivity and functionality of steroids. Furthermore, we discuss prospective research directions for CYP450s in plant steroid biosynthesis, aiming to provide a comprehensive and up-to-date overview of CYP450s involved in plant steroid metabolism. This review is intended to give novel insights for deciphering additional steroid biosynthetic pathways and advancing their biotechnological applications.