具有独特化学结构和生理活性的天然产物生物合成途径的发现与合成机制的阐明是当今微生物药物深度研发并快速推向应用的核心环节，并已成为现代微生物学最为关注的重要领域之一。本申请以分离自我国海南热带海域红树林根际土壤产生多个阿扎霉素（Azalomycin）F系列化合物的链霉菌Streptomyces sp. 211726为主要研究材料，利用申请人前期在剑桥大学对来自内陆的链霉菌Streptomyces sp. DSM4137产生单一同类化合物的研究积累，综合运用分子遗传学、化学生物学和生物信息学等手段对其结构和生物合成基因簇进行比较研究，阐明该类化合物生物合成机制，为其组合生物合成提供精确的"分子装配线路图"。同时，通过对关键基因的体内外研究，解析导致该类化合物结构多样性差异的内在原因，为更加有的放矢地利用天然产物生物合成途径来主动创新这类微生物药物提供理论和技术基础。

Discovery and characterisation of biosynthetic pathway and mechanism of natural products with specific structures and bioactivities is the key for its further research and rapid application, and it has now been one of the most attractive field in the mordern Microbiology. More than 10 Azalomucin F serial polyhydroxy macrolactones, the metabolites of Streptomyces sp. 211726 isolated from mangrove rhizosphere soil in Hainan province of China, showed a remarkable antifungal and promising anti-tumor activities. My previous investigation carried out in the University of Cambridge has identified the terrestrial Streptomyces sp. DSM4137 as an independent producer of unique Azalomycin F4 but its syhtnetic pathway is still unknown. The twins of Azalomycin F producer strains from different geographical features open a door for us to understand its biosynthetic mechanism through comparative studies. Meanwhile, the more diversity of structure from 211726 could provide us an opportunity to find the crucial enzyme that is responsible for the diversity of Azalomucin F, which would result in creating novel Azalomycin derivatives by combinatorial approach. Thus, we propose here to undertake work on elucidation of the biosynthetic mechanism of Azalomycin F and the critical step for generating a variety of targeted derivatives reasonably.