Zou Li-Qiu, Kuang Xue-Jun, Sun Chao, Chen Shi-Lin
Institute of Medicinal Plant Development, China Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2016 Nov;41(22):4119-4123. doi: 10.4268/cjcmm20162206.
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.
阐明天然产物的生物合成途径不仅是草药基因组学的主要目标，也是天然产物合成生物学的坚实基础。在此，本文综述了该领域的最新进展，并提出了阐明天然产物生物合成途径的策略。首先，应基于关于化学反应的已知知识、已鉴定化合物的信息以及同位素示踪研究，建立一条假定的生物合成途径。其次，通过共表达分析和/或基因簇挖掘筛选出可能参与生物合成途径的候选基因。最后，将所有候选基因在宿主中进行异源表达，然后通过活性测定对参与生物合成途径的酶进行表征。有时，可通过RNAi或VIGS技术进一步研究该酶在原始植物中的功能。了解天然产物的生物合成途径将有助于通过合成生物学提供新的先导化合物，并为草药分子育种提供“功能标记”，从而推动中药农业的发展。
