CYP450s参与的植物甾体生物合成途径研究进展

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

摘要:

植物甾体化合物种类繁多，具有重要的生理作用，且在抗肿瘤、抗病毒、抗菌、抗炎、降血糖血脂、保肝、免疫调节等方面药理活性显著，是创新药物的重要来源。细胞色素P450 (cytochrome P450s, CYP450s)超家族是一类含亚铁血红素的酶，它们能够进行极其显著的区域特异性和立体特异性氧化反应。CYP450s在植物甾体化合物结构氧化修饰中发挥关键作用。本文全面概述了已鉴定功能的CYP450蛋白，它们参与植物甾体化合物的骨架形成(如C-14脱甲基反应、侧链降解反应等)及骨架与侧链修饰。另外，还基于甾体骨架及侧链的不同结构，重点总结了参与Δ22-甾醇、油菜素甾醇、胆固醇衍生物、醉茄内酯等甾体化合物生物合成途径的CYP450s的研究进展及氧化修饰对甾体活性及功能的影响。最后，还对未来CYP450s在植物甾体生物合成中的研究方向进行了讨论展望，为参与植物甾体化合物生物合成的CYP450s提供一个新的、全面的概览，并为未来更多甾体化合物生物合成途径的解析提供思路及借鉴。

Abstract:

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.