格尔德霉素生物合成的调控基因.PDFVIP

生 物 工 程 学 报 Chin J Biotech 2008, May 25; 24(5): 717-722 Chinese Journal of Biotechnology ISSN 1000-3061 cjb@ © 2008 Institute of Microbiology, CAS CSM, All rights reserved 研究报告 格尔德霉素生物合成的调控基因 赫卫清, 雷健, 刘玉瑛, 王以光 中国医学科学院/ 中国协和医科大学医药生物技术研究所, 卫生部抗生素生物工程重点实验室, 北京 100050 摘 要: 从吸水链霉菌 17997 中克隆了格尔德霉素(Geldanamycin, Gdm)生物合成酶基因簇, 通过生物信息学分析发现 两个LAL(Large ATP-binding regulators of the LuxR family) 家族的调控基因gdmRI 和gdmRII , 基因阻断和基因回复实验 证实这两个基因产物都正调控Gdm 的生物合成。 关键词: 格尔德霉素(Geldanamycin, Gdm), 调控基因, 基因阻断 Regulatory Genes of Geldanamycin Biosynthesis Weiqing He, Jian Lei, Yuying Liu, and Yiguang Wang Key Laboratory of Biotechnology of Antibiotics of Ministry of Health , Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100050, China Abstract: Two LAL family regulatory genes, gdmRI and gdmRII, were identified in the geldanamycin biosynthetic gene cluster of Streptomyces hygroscopicus 17997. Disruption of the two regulatory genes resulted in absolute elimination of geldanamycin biosynthesis. The complementation experiments using a single wild-type gene could restore geldanamycin production. These results indicated that both gdmRI and gdmRII were positive regulatory genes of the geldanamycin biosynthesis. Keywords: geldanamycin (Gdm), regulatory gene, gene disruption 热休克蛋白90(Heat shock protein 90, Hsp90)参 Gdm 生物合成酶基因簇[5], 通过生物信息学分析, 与调控、维持细胞内多种蛋白的构象和功能, 也是 从中发现两个调节基因, gdmRI 和gdmRII 。分析二者 多种信号传导蛋白的分子伴侣, 是近年来抗肿瘤研 蛋白序列发现在C 端均含有LuxR 类型的螺旋-转角 究中发现的极具应用价值的新靶点[1] 。格尔德霉素 -螺旋(Helix-turn-helix, HTH)的DNA 结合