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链霉菌分子生物学研究组

组长：谭华荣，博士 研究员

电话：010-64807461

Email: Tanhr@sun.im.ac.cn

 

 

研究方向：

研究方向为链霉菌次生代谢和发育分化的分子调控。关键词: 链霉菌,次生代谢,发育分化,分子调控。

研究内容：

      以链霉菌为模式系统，研究发育分化中基因的时空表达及其作用的分子机制，为揭示生命现象的基本规律及与抗生素生物合成的关系提供理论依据。研究微生物次生代谢的生物合成途径及其基因的特异调控和全局调控，为定向改良生产菌的生产能力和获得新的代谢产物提供理论指导。

     2007年度主要取得如下进展：

    1). 与链霉菌分化和代谢有关的hppD基因的研究: hppD是链霉菌酪氨酸分解代谢中一个重要的调控基因。4—羟基苯丙酮酸氧化酶(HppD)催化酪氨酸的分解代谢的第二步反应，对于贫瘠条件下生长的微生物来说，这步反应可以直接供给菌体生长所需要的碳源和能源物质。转录分析表明hppD的表达受到两个与其邻近的正调控因子-HpdA和负调控因子-ScrX（或称HpdR）的调控。这种初级代谢的复杂调控不但间接地影响了相关次生代谢产物（如放线紫红素）的生物合成，而且也影响了链霉菌的正常生长和发育。有关结果发表在本领域（微生物学领域）顶级刊物（Molecular Microbiology, 65: 1064-1077, 2007）。

      2). 链霉菌发育分化基因—whiI及其靶基因的研究：whiI是天蓝色链霉菌发育分化中控制孢子分隔的一个重要的调控基因，其调控蛋白类似于细菌双组分系统，但失去了典型磷酸化域的保守特征。该基因阻断导致的突变株在基本培养基上几乎不能生长，而在适当培养基中加入肌醇，并随着肌醇浓度的增加，链霉菌能很好的生长和发育分化。上述有关结果已发表在国际微生物领域的核心期刊《Journal of Bacteriology, 189:2873-2885, 2007》上，更深入的研究工作正在进行之中。

      3). 圈卷产色链霉菌尼可霉素生物合成相关基因－sanN、sanM和sanT的功能研究：基因阻断和互补实验证明sanN和sanM和sanT是圈卷产色链霉菌尼可霉素生物合成所必需的。生化实验表明：SanM通过与SanN互作，催化POHIV的合成；SanN的活性则不依赖于SanM与SanN的互作，其催化吡啶酰CoA生成吡啶醛；在发酵培养基中添加前体物尼克酸时sanL 或sanK突变株可大量合成新型尼可霉素（PX和PZ）。初步实验证据表明，尼可霉素PX和PZ具有很强的抗真菌活性，并且比野生型菌株产生的尼可霉素X和Z具有更好的稳定性。SanT蛋白是一个双结构域蛋白，ACP结构域的第33位丝氨酸翻译后修饰了磷酸泛酰疏基乙胺（Ppant）。ATP结构域可以催化尼可霉素肽基部分前体4-吡啶-2-氧-4-羟-异戊酸（POHIV）转氨生成吡啶同型苏氨酸（PHT）。 两个结构域独立起作用，但都是尼可霉素生物合成所必需的。 上述部分结果已在Biochemical and Biophysical Research Communications上发表研究论文2篇。

课题组成员：

课题组长

             谭华荣，博士 研究员

1991年毕业于英国东英大学和英国John Innes研究所，获博士学位。现任微生物研究所党委书记兼副所长，学位委员会主任。中国微生物学会副理事长。《微生物学报》主编，《遗传学报》副主编，1994年入选中科院首批“百人计划”，1999年获“国家杰出青年基金”资助。主要从事微生物发育分化和次生代谢分子调控的研究。

         电话：010－64807461
         E-mail: Tanhr@sun.im.ac.cn

副研究员

刘  钢   杨海花

助理研究员

田宇清      

博士研究生：

牛国清   贾良辉   凌洪博   盖玉玲   谢周杰   胡  坤   李艳华    潘园园    张国华    王琳淇    严晓华   
廖国建   李  睿

硕士研究生

李金娥   何希宏    梁   亮   张  悦    张树利

重要成果


论著

  1. Gangming Xu#, Juan Wang#, Linqi Wang, Xiuyun Tian, Haihua Yang, Keqiang Fan, Keqian Yang*, and Huarong Tan*. 2010. 'Pseudo' gamma-butyrolactone receptors respond to antibiotic signals to coordinate antibiotics biosynthesis. Journal of Biological Chemistry (online) doi:10.1074/jbc.M110.143081 (# shared the first author) (IF 5.328)
  2. Haihua Yang, Yang An, Linqi Wang, Shuli Zhang, Yue Zhang, Yuqing Tian, Gang Liu, Huarong Tan*. 2010. Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor. Microbiology-SGM. [Epub ahead of print] (IF 3.025)
  3. Guohua Zhang, Yuqing Tian, Kun Hu, Chi Feng and Huarong Tan*. 2010. SCO3900, co-transcripted with three downstream genes, is involved in the differentiation of Streptomyces coelicolor. Current Microbiology. 60(4): 268-273 (IF 1.330)
  4. Xihong He, Rui Li, Yuanyuan Pan, Gang Liu* and Huarong Tan*. 2010. SanG, a transcriptional activator, controls nikkomycin biosynthesis through binding to the sanN-sanO intergenic region in Streptomyces ansochromogenes.  Microbioogy-SGM. 156:828 (IF 2.841)
  5. Guojian Liao, Jin’e Li, Lei Li, Haihua Yang, Yuqing Tian, Huarong Tan*. 2010. Cloning, reassembling and integration of the entire nikkomycin biosynthetic gene cluster into Streptomyces ansochromogenes lead to an improved nikkomycin production. Microbial Cell Factories. 9:6, doi:10.1186/1475- 2859-9-6 (IF 3.338)
  6. Rui Li, Gang Liu, Zhoujie Xie, Xihong He, Wenqing Chen, Zixin  Deng and Huarong Tan*. 2010. PolY, a transcriptional regulator with ATPase activity, directly activates transcription of polR in polyoxin biosynthesis in Streptomyces cacaoi. Molecular Microbiology. 75(2): 349-364. (IF 5.213)
  7. Shuli Zhang#, Bo Liu#, Haihua Yang*, Yuqing Tian, Gang Liu, Lei Li and Huarong Tan*. 2010. Characterization of EndoTT, a novel single-stranded DNA specific endonuclease from Thermoanaerobacter tengcongensis. Nucleic Acids Research. (accepted). (IF 6.878)
  8. Guojian Liao, Jin’e Li, Lei Li, Haihua Yang, Yuqing Tian and Huarong Tan*. 2009. Selectively improving nikkomycin Z production by blocking the imidazolone biosynthetic pathway of nikkomycin X and uracil feeding in Streptomyces ansochromogenes. Microbial Cell Factories. 8:61, doi:10.1186/1475-2859-8-61. (IF 3.338)
  9. Rui Li#, Zhoujie Xie#, Yuqing Tian, Haihua Yang, Wenqing Chen, Delin You, Gang Liu, Zixin Deng*, and Huarong Tan*. (2009). polR, a pathway-specific transcriptional regulatory gene, positively controls polyoxin biosynthesis in Streptomyces cacaoi var. Asoensis. Microbiology-SGM 155:1819-1831 (IF 2.841)
  10. Yuanyuan Pan#, Gang Liu#, Haihua Yang, Yuqing Tian and Huarong Tan*. (2009). The pleiotropic regulator AdpA-L directly controls the pathway-specific activator of nikkomycin biosynthesis in Streptomyces ansochromogenes. Molecular Microbiology (#shared the first author) 72(3): 710-723. (IF 5.462)
  11. Linqi Wang#, Xiuyun Tian#, Juan Wang, Haihua Yang, Keqiang Fan, Gangming Xu, Keqian Yang*, and Huarong Tan*. (2009). Autoregulation of antibiotic biosynthesis: direct binding of jadomycin to an atypical response regulator. Proceedings of the National Academy of Sciences of the United States of America (#shared the first author) 106(21): 8617-8622. (IF 9.598)
  12. Wenqing Chen, Tingting Huang, Xinyi He, Qingqing Meng, Delin You, Linquan Bai, Jialiang Li, Mingxuan Wu, Rui li, Zhoujie Xie, Huchen Zhou, Xiufen Zhou, Huarong Tan*, and Zixin Deng*. (2009).Characterization of the polyoxin biosynthetic gene cluster from Streptomyces cacaoi and engineered production of polyoxin H. The Journal of Biological Chemistry 284(16): 10627-10638 (IF 5.581)
  13. Yanhua LiJihui Zhang , Huarong Tan*.2008. Identification of a Nitroalkane oxidase gene: naoA related to the growth of Streptomyces ansochromogenes.Current Microbiology 57: 588-592. (IF 1.167)
  14. Hongbo Ling, Guojun Wang, Jin’e Li, Huarong Tan*. 2008. sanN encoding a dehydrogenase is essential for nikkomycin biosynthesis in Streptomyces ansochromogenes. Journal of Microbiology and Biotechnology 18(3):397-403. PDF (IF 2.062)
  15. Yue Zhang, Linqi Wang, Shuli Zhang, Haihua Yang* and Huarong Tan. hmgA, transcriptionally activated by HpdA, influences the biosynthesis of actinorhodin in Streptomyces coelicolor. FEMS Microbiology Letters 280:219-225.2008. PDF (IF 2.274)
  16. Liang Liang, Xihong He, Gang Liu* and Huarong Tan*. The role of a purine-specific nucleoside hydrolase in spore germination of Bacillus thuringiensis. Microbiology-SGM 154:1333-1340. 2008. PDF (IF 3.110)
  17. Haihua Yang, Linqi Wang, Zhoujie Xie, Yuqing Tian, Gang Liu, Huarong Tan*. The tyrosine degradation gene hppD is transcriptionally activated by HpdA and repressed by HpdR in Streptomyces coelicolor, while hpdA is negatively autoregulated and repressed by HpdR. Molecular Microbiology. 65 : 1064-1077, 2007.
  18. Yuqing Tian, Kay Fowler, Kim Findlay, Huarong Tan* & Keith F. Chater*. An unusual response regulator influences sporulation at early and late stages in Streptomyces coelicolor. Journal of Bacteriology. 189 : 2873-2885, 2007.
  19. Hongbo Ling, Guojun Wang, Yuqing Tian, Gang Liu and Huarong Tan*. SanM catalyzes the formation of 4-pyridyl-2-oxo-4-hydroxyiso- valerate in nikkomycin biosynthesis by interacting with SanN. Biochemical and Biophysical Research Communications. 361: 196-201, 2007.
  20. Jia Lianghui , TianYuqing, Tan Huarong*. SanT, a bidomain protein, is essential for nikkomycin biosynthesis of S. an sochromogenes. Biochemical and Biophysical Research Communications. 362: 1031-1036, 2007.
  21. Zhoujie Xie, Wenli Li, Yuqing Tian, Gang Liu & Huarong Tan*. Identification and characterization of sawC, a whiA-like gene, essential for sporulation in Streptomyces ansochromogenes. Archives of Microbiology. 188: 575-582, 2007

专利 (Patent)


谭华荣 刘 钢 尼可霉素生物合成调控基因及其编码蛋白与表达工程菌. 2007. 授权号: ZL 2004 1 0058411.2.