《生命科学》 2011, 23(9): 891-899

天然产物类药物的合成生物学研究

黄　伟，王健博，唐功利^*

(中国科学院上海有机化学研究所，生命有机化学国家重点实验室，上海 200032)

摘　要：摘　要：结构复杂多样的天然产物是现代药物的重要组成部分和新药发现的重要源泉。建立在基因工程及代谢工程、合成化学、基因组学、系统生物学等学科基础上的合成生物学研究对于结构复杂的天然产物类药物研究有特殊的意义。核心是通过在发酵友好、高效的微生物中设计、构建目标化合物的生物合成途径，经系统地调控和优化由重组微生物发酵生产来源稀缺的天然产物类药物或前体。该方法是不远的将来解决来源、成本与环境、资源协调问题最好的途径之一，也是解决海洋天然产物或特殊生境微生物药物面临的如何持续供应化合物这一个瓶颈问题的最佳选择。该文将对天然产物类药物合成生物学研究涉及的主要策略和重要进展进行阐述。
关键词：天然产物；合成生物学；生物合成；基因簇；异源表达

Synthetic biology toward medicinal natural products

HUANG Wei， WANG Jian-Bo， TANG Gong-Li^*

(State Key Laboratory of Bio-organic and Natural Products Chemistry，Shanghai Institutes of Organic Chemistry， Chinese Academy of Sciences， Shanghai 200032， China)

Abstract: Abstract: Natural products are the major sources of current clinical drugs and further discovery of new drugs. Based on genetic engineering， metabolic engineering， chemical synthesis， genomics and systematic biology， synthetic biology provide a significant driving force to develop complex drugs originated from natural products. Efforts have been focused on the design， assembly of biosynthetic pathways and heterologous expression the artifical gene cluster in fermention-friendly hosts to produce medicinal natural products or precursors. This method offered a framework， maybe the best choice， for the supplement of complex natural products， especially for the trace compounds from marine or microorganisms in special ecotope. This review describes the major strategies and recent developments of synthetic biology toward medicinal natural products.
Key words: natural product; synthetic biology; biosynthesis; pathway; gene cluster; heterologous expression