重要抗生素生物合成机制的解析是当今药物深度研发的核心环节，对已广泛应用于临床治疗的庆大霉素和西索霉素生物合成机制进行全面清晰的阐明是利用组合生物合成和合成生物学方法进行定向优化和创新氨基糖苷类抗生素的必要前提。基于前期实验中的研究发现，强烈地暗示着庆大霉素与西索霉素的生物合成途径可能存在着某种"耦合"，从而引发庆大霉素与西索霉素的共合成。因此，本申请以庆大霉素野生型产生菌棘孢小单孢菌Micromonospora echinospora ATCC15835为研究材料，拟综合运用分子遗传学、化学生物学和生物信息学等方法，开展关于庆大霉素与西索霉素耦合生物合成机制的研究，为有的放矢地利用天然产物生物合成途径来改造氨基糖苷类抗生素从而实现老药新用，更好地为人类健康服务。

Elucidation of biosynthetic mechanism of important antibiotic is a key for its further research and application. Comprehensive characterisation of clinically and wildly used gentamicin and sisomicin is a necessary precondition for directed optimization and creation of aminoglycoside antibiotics through combinatorial biosynthesis and synthetic biology. The results of our/others preliminary studies indicated strongly that certain coupling pathway probably shared by gentamicin and sisomicin biosynthesis resulting in their co-biosynthesis. Thus, we propose here to undertake work on elucidation of the coupling biosynthetic mechanism of gentamicin and sisomicin in Micromonospora echinospora ATCC15835 by means of molecular biological, chemical biological and bioinformatic approachs to target renew the "old medicine" of aminoglycoside antibiotics by modification of natural product biosynthetic pathway, and aim for human health.