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hupowangyu
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Aurovertin类化合物是由特殊环境真菌齿梗孢霉产生的一类抗生素，在结构中含有特征性的2,6-二恶二环[3,2,1]-辛烷环结构，使其具有独特的活性，抑制细菌中ATP合酶的合成。由于特殊环境真菌操作困难，此类化合物的生物合成研究并未深入。本项目通过测序齿梗孢霉基因组序列，结合生物信息学分析找到合成aurovertin B的基因簇。利用建立的宿主菌自身遗传操作系统和构建模式真菌构巢曲霉系统，两个系统相结合来阐明aurovertin B的生物合成途径，进而构建aurovertin B的代谢途径。通过体外克隆表达合成2,6-二恶二环[3,2,1]-辛烷环结构的关键酶的基因，进行酶促反应，研究其反应机理，解析该特殊环结构的形成机制。本研究的思路和涉及的关键实验技术将为从特殊环境真菌中阐明活性天然产物的生物合成途径提供有价值的参考，为定向合成和改造此类天然产物提供理论依据。 Aurovertins are a family of antibiotics produced by fungus Calcarisporium arbuscular with special features of 2,6-dioxabicyclo[3.2.1]octanes in structures. They have unique biological activities which can inhibit the synthesis of ATPase in many bacterial species. Researches on the biosynthesis of aurovertins have been impeded since it is hard to handle this fungus genetically. We sequenced this strain and found the biosynthetic gene cluster of aurovertin B by bioinformatic analysis. Then, we will characterize the biosynthetic pathway of aurovertin B via the established genetic system from C. arbuscular in combination with model genetic system Aspergillus nidulans.Furthermore, the metabolic pathway of aurovertin B will be created in A. nidulans. For the understanding the mechanism of ring formation of 2,6-dioxabicyclo[3.2.1]octanes, we will characterize the function of the key genes involving in the ring formation via enzymatic reaction in vitro.The idea and key techniques in our research will provide a new way for the study on the biosynthesis of bioactive natural products from difficult fungi and good supporting for the oriented synthesis of the similar compounds in principle. |
2楼2020-06-23 16:23:26