井冈霉素生物合成基因簇的功能分析及井冈胺A的工程化生产
Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A.
作者信息
Bai Linquan, Li Lei, Xu Hui, Minagawa Kazuyuki, Yu Yi, Zhang Yirong, Zhou Xiufen, Floss Heinz G, Mahmud Taifo, Deng Zixin
机构信息
Laboratory of Microbial Metabolism and School of Life Science & Biotechnology, Shanghai Jiaotong University, Shanghai 200030, China.
出版信息
Chem Biol. 2006 Apr;13(4):387-97. doi: 10.1016/j.chembiol.2006.02.002.
Abstract
A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VAL-A) biosynthesis revealed 16 structural genes, 2 regulatory genes, 5 genes related transport, transposition/integration or tellurium resistance; another 4 genes had no obvious identity. The VAL-A biosynthetic pathway was proposed, with assignment of the required genetic functions confined to the sequenced region. A cluster of eight reassembled genes was found to support VAL-A synthesis in a heterologous host, S. lividans 1326. In vivo inactivation of the putative glycosyltransferase gene (valG) abolished the final attachment of glucose for VAL production and resulted in accumulation of the VAL-A precursor, validoxylamine, while the normal production of VAL-A could be restored by complementation with valG. The role of valG in the glycosylation of validoxylamine to VAL-A was demonstrated in vitro by enzymatic assay.
摘要
对参与井冈霉素A（VAL-A）生物合成的吸水链霉菌5008进行的45 kb DNA测序分析揭示了16个结构基因、2个调控基因、5个与转运、转座/整合或碲抗性相关的基因；另外4个基因没有明显的同源性。提出了VAL-A生物合成途径，所需的遗传功能被定位到测序区域。发现一组八个重新组装的基因在异源宿主变铅青链霉菌1326中支持VAL-A的合成。推定的糖基转移酶基因（valG）的体内失活消除了VAL生产中葡萄糖的最终附着，并导致VAL-A前体井冈霉胺的积累，而通过用valG互补可以恢复VAL-A的正常生产。通过酶促测定在体外证明了valG在井冈霉胺糖基化形成VAL-A中的作用。
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