化学基元组学与药物创新

Chemomics and drug innovation

化学基元组学(chemomics)是与化学信息学、生物信息学、合成化学等学科相关的交叉学科.生物系统从内源性小分子(天然砌块)出发,通过酶催化的化学反应序列制造天然产物.生物系统通过化学反应和天然砌块向目标天然产物"砌入"一组原子,这样的一组原子称为化学基元(chemoyl).化学基元组(chemome)是生物组织中所含有的化学基元的全体.化学基元组学研究各种化学基元的结构、组装与演化的基本规律.在生存压力和繁衍需求的驱动下,生物系统已经进化出有效手段来合成天然产物以应付环境的变化,并产生了丰富多彩的生物和化学多样性.近年来,人们意识到药物创新的瓶颈之一是药物筛选资源的日益枯竭.化学基元组学可以解决这个瓶颈问题,它通过揭示生物系统制备化学多样性的规律,发展仿生合成方法制备类天然化合物库(quasi natural product libraries)以供药物筛选.本文综述了化学基元组学的主要研究内容及其在药物创新各领域中的潜在应用.

Chemomics is an interdisciplinary study using approaches from chemoinformatics, bioinformatics, synthetic chemistry, and other related disciplines. Biological systems make natural products from endogenous small molecules （natural product building blocks） through a sequence of enzyme catalytic reactions. For each reaction, the natural product building blocks may contribute a group of atoms to the target natural product. We describe this group of atoms as a chemoyl. A chemome is the complete set of chemoyls in an organism. Chemomics studies chemomes and the principles of natural product syntheses and evolutions. Driven by survival and reproductive demands, biological systems have developed effective protocols to synthesize natural products in order to respond to environmental changes; this results in biological and chemical diversity. In recent years, it has been realized that one of the bottlenecks in drug discovery is the lack of chemical resources for drug screening. Chemomics may solve this problem by revealing the rules governing the creation of chemical diversity in biological systems, and by developing biomimetic synthesis approaches to make quasi natural product libraries for drug screening. This treatise introduces chemomics and outlines its contents and potential applications in the fields of drug innovation.