近十年天然产物药物的生物合成研究进展  

Research advances in biosynthesis of natural product drugs within the past decade

作　　者：冯金 潘海学 唐功利[1,2] FENG Jin;PAN Haixue;TANG Gongli(School of Chemistry and Materials Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,Zhejiang,China;State Key Laboratory of Chemical Biology,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China)

机构地区：[1]中国科学院大学杭州高等研究院,化学与材料科学学院,浙江杭州310024 [2]中国科学院上海有机化学研究所,生命过程小分子调控全国重点实验室,上海200032

出　　处：《合成生物学》2024年第3期408-446,共39页Synthetic Biology Journal

基　　金：国家自然科学基金(32070065)。

摘　　要：天然产物一直是潜在的先导药物的重要来源,天然产物及其结构类似物在历史上对疾病治疗做出了重大贡献,特别是对癌症和传染病的治疗。在过去两百年的时间里,天然产物的发现和研究经历了巨大的变化,由传统的分离鉴定为主的经典研究方法转为了基因组时代的多学科组合研究。虽然近二十年发现和挖掘了丰富的活性天然产物,但与自然界中巨大的天然产物合成潜力相比仍有不足,庞大的陆地和海洋天然产物资源尚待开发。同时,与传统的化学合成分子相比,天然产物具有丰富的骨架多样性和结构复杂性,在新药发现中展现了巨大的优势。虽然在天然产物的新药创新方面仍面临着种种挑战,但新的分析技术和挖掘策略的出现有望迎来天然产物发现的新阶段。本文总结了近十年(2014年1月—2023年10月)美国食品药品监督管理局批准成药的天然产物及源自天然产物的半合成药物,并对其中纯天然产物来源分子、重要的半合成天然产物前体的生物合成研究进展进行了详细总结。此外还简要总结了一些FDA批准的老药在过去十年中取得的重要生物合成研究进展。期望通过对成药天然产物生物合成途径及机制的深入理解,为更多天然产物创新药物的发现和研究提供借鉴。Natural products have long been considered as an important source for potential drugs.In history,natural products and their structural analogs have contributed substantially to the treatment of various diseases,especially cancers and infectious diseases.After a long history of applications,people have gradually begun to explore active ingredients in natural products that truly exert therapeutic effects,and discovered a series of functional compounds,such as morphine,quinine,ephedrine,etc.Over the past two hundred years,the discovery and research of natural products has undergone tremendous changes,from traditional identification and isolation methods to multidisciplinary approaches in the modern genomic era.Strategies for discovering natural products and tools for their prediction have been developed continuously.Although many novel and active natural products have been mined and discovered in the past two decades,considering the huge reserve of natural products in nature,a large number of genes or gene clusters encoding key enzymes for the biosynthesis of natural products have not yet been characterized,and both terrestrial and marine natural product resources are to be explored.Compared with traditional chemically synthesized molecules,natural products possess diverse skeletons for structural complexity,which have shown remarkable advantages in the discovery of new drugs.While there are still many challenges in discovering new drugs from natural products,such as the effective mining of molecules with new structural features,identification and isolation of functional natural products with trace abundance,derivatization of natural product analogs for exploring connections between their structures and activities,and the complete synthesis of complicated active natural products at large scales,etc.,the emergence of novel analytical technologies and mining strategies is expected to substantially renovate natural product discovery.This review comments on the natural product drugs and semisynthetic drugs derived from

关 键 词：天然产物 半合成药物 新药发现 生物合成 

分 类 号：Q81[生物学—生物工程]