天然产物生物合成途径解析策略

天然产物合成途径解析既是本草基因组学研究的主要目标,也是天然产物合成生物学研究的重要基石。该文综述了近期相关领域的研究进展,提出了天然合成生物合成途径解析的一般策略:即首先通过同位素示踪实验结果和化学反应原理、已分离鉴定的中间产物等信息推测出可能的生物合成途径;然后利用共表达分析和/或基因簇发掘筛选出途径中的候选基因;最后对所有候选基因进行异源表达和酶活性检测确定参与代谢途径的酶,并可在原物种中进行该酶基因的抑制或过表达研究,进一步确认该酶在原物种体内的功能。天然产物生物合成途径的解析将有助于通过合成生物学技术为新药研发提供新的化合物来源,并可为中草药的分子育种研究提供"功能性分子标记",加速优良品种的选育,推动中药农业的发展。

Strategies of elucidation of biosynthetic pathways of natural products

Elucidation of the biosynthetic pathways of natural products is not only the major goal of herb genomics, but also the solid foundation of synthetic biology of natural products. Here, this paper reviewed recent advance in this field and put forward strategies to elucidate the biosynthetic pathway of natural products. Firstly, a proposed biosynthetic pathway should be set up based on well-known knowledge about chemical reactions and information on the identified compounds, as well as studies with isotope tracer. Secondly, candidate genes possibly involved in the biosynthetic pathway were screened out by co-expression analysis and/or gene cluster mining. Lastly, all the candidate genes were heterologously expressed in the host and then the enzyme involved in the biosynthetic pathway was characterized by activity assay. Sometimes, the function of the enzyme in the original plant could be further studied by RNAi or VIGS technology. Understanding the biosynthetic pathways of natural products will contribute to supply of new leading compounds by synthetic biology and provide "functional marker" for herbal molecular breeding, thus but boosting the development of traditional Chinese medicine agriculture.