Research advances in biosynthesis of natural product drugs within the past decade
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 natural products approved by the U.S.Food and Drug Administration within the past decade from January 2014 to October 2023,and provides an overview on the research progress on the biosynthesis of these natural products and their precursors.In addition,important progress in the biosynthesis of some drugs approved by FDA before is also briefly summarized.An in-depth understanding of the biosynthetic pathways and mechanisms underlying their efficacy is expected to provide valuable insights for the discovery and research of more new drugs in the future.
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