《生命科学》 2021, 33(12): 1510-1519

合成生物学助力天然产物的高效合成及创新发现

池豪铭 , 刘天罡^*

武汉大学药学院，组合生物合成及新药发现教育部重点实验室，武汉 430071

摘　要：

天然产物是候选药物以及药物先导化合物的重要来源，但传统的天然产物生产方式及新天然产物发现的速度和数量日益无法满足社会的巨大需求。随着合成生物学各方面技术的发展，合成生物学在天然产物高产和发现两个领域上的新策略、新方法、新应用应运而生，尤其在复杂天然产物的高效生物全合成、天然产物复杂前体结构的化学半合成、沉默天然产物的高通量挖掘等方面有着里程碑式的发展。该文讨论并总结了目前合成生物学在天然产物研究领域所面临的挑战和机遇，为如何解决复杂天然产物合成机制难以解析、基于微生物发酵的天然产物“出口”受限等问题提出了一些思考和建议。

通讯作者：刘天罡 , Email:liutg@whu.edu.cn

Synthetic biology promotes efficient production and innovative discovery of natural products

CHI Hao-Ming , LIU Tian-Gang^*

Key Laboratory of Combinational Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China

Abstract:

Natural products are significant sources of drug candidates and lead compounds, but the traditional approaches to natural product manufacture and the speed and quantity of new natural product discovery are failing to meet the enormous needs of society. With the advancement of technologies in all aspects of synthetic biology, new strategies, new methods, and new applications of synthetic biology in the two fields of natural product high yield and discovery have emerged, especially in the areas of efficient biological total synthesis of complex natural products, chemical semi-synthesis of complex precursor structures of natural products, and high-throughput mining of silent natural products. This review discusses and summarizes the challenges and opportunities of synthetic biology in the natural product research field, and provides some considerations and suggestions on how to solve the difficulties in resolving the mechanisms of complex natural product synthesis and the limitations of "export" of natural products based on microbial fermentation.

Communication Author：LIU Tian-Gang , Email:liutg@whu.edu.cn