新的氧化偶氮类天然产物的发掘、合成途径的解析与应用

氧化偶氮类化合物尤其是芳香族氧化偶氮类化合物在材料、化工、药物、农药等领域具有很大的应用前景。目前被发现的氧化偶氮类天然产物尤其是芳香族氧化偶氮类天然产物数量极其稀少，它们的生物合成途径尤其是氧化偶氮基团的生物合成机制至今仍然不清楚。本课题组分离得到了3个芳香族氧化偶氮类天然产物氧化偶氮霉素A、B、C，克隆了它们的合成基因簇azo基因簇，发现了催化氧化偶氮基团生物合成的酶AzoC。本项目首先通过生物信息学分析发掘新的氧化偶氮类天然产物合成基因簇；通过分子遗传学技术激活菌株中的目标基因簇；分离纯化新的氧化偶氮类天然产物；通过生物化学表征解析氧化偶氮类天然产物的生物合成途径，尤其氧化偶氮基团的合成。本项目的研究结果一方面丰富氧化偶氮类天然产物库、解析氧化偶氮基团的合成机制，一方面建立从生物信息学出发发掘新天然产物的策略。

Azoxy compounds, especial aromatic azoxy compounds, are widely used as dyes, reducing agents, chemical stabilizers, polymerization inhibitors, therapeutic agents, and energetic materials. To date, only a few natural azoxy compounds, especial natural aromatic azoxy compounds, have been reported. Little is known about their biosyntheses. The biosynthetic mechanism of azoxy group remains a mystery. Our group have identified three natural aromatic azoxy compounds, azoxymycins A, B, and C; cloned their biosynthetic gene cluster, azo gene cluster; and characterized AzoC, the enzyme involved in azoxy group biosynthesis. In this project, we will clone new natural azoxy compound biosynthetic gene clusters by bioinformatics technologies; activate the target gene clusters by molecular genetics technologies; identify new natural azoxy compounds; unveil the biosynthetic pathways of new natural azoxy compounds; and characterize the biosynthetic mechanism of azoxy groups. Our results will not only expand the library of natural aromatic azoxy compound and our understanding of azoxy group biosynthetic mechanism, but also develop a strategy for identification of new natural products based on bioinformatics.