白林泉
1、井冈霉素/有效霉素的生物合成。2、安莎类抗生素的生物合成机理与组合生物合成改造。3、次生代谢产物生物合成基因资源挖掘。
个性化签名
- 姓名:白林泉
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者
- 职称:-
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学科领域:
微生物学
- 研究兴趣:1、井冈霉素/有效霉素的生物合成。2、安莎类抗生素的生物合成机理与组合生物合成改造。3、次生代谢产物生物合成基因资源挖掘。
白林泉,1992年毕业于山东大学微生物系,获学士学位。1995年毕业于华中农业大学微生物专业,获硕士学位。1998年毕业于华中农业大学分子生物学专业,获理学博士学位。1999年至2002年4月在美国华盛顿大学化学系从事博士后研究。2002年4月回国到上海交通大学生命科学技术学院工作。2006年至2007年初在德国Tuebingen大学微生物研究所从事生物合成调节方面的合作研究。2007年入选教育部“新世纪优秀人才支持计划”,2008年初晋升为教授。现任职于上海交通大学微生物代谢教育部重点实验室。共发表13篇SCI研究论文,相关研究成果入选“2006年度中国高等学校十大科技进展”、获得教育部“2007年度自然科学二等奖”。
研究方向:
1、井冈霉素/有效霉素的生物合成
抗水稻纹枯病氨基环醇井冈霉素是重要的农用抗生素,也是我国开发最为成功的抗生素之一。在前期研究中,我们克隆了井冈霉素的生物合成基因簇并建立了产生菌的遗传操作系统。在此基础上,我们正在开展结构基因的功能、井冈霉素产生的温度调节和代谢工程产量提高方面的研究。井冈霉素产生菌的基因组学研究也在进行之中。
2、安莎类抗生素的生物合成机理与组合生物合成改造
安莎类抗生素是一类大环内酰胺类聚酮化合物,包含利福霉素、格尔登素、安丝菌素、萘霉素等,具有抗肿瘤、抗结核杆菌、抗细菌等多种生理活性。安莎类抗生素在基本骨架的合成方面具有一定相似性,产生了部分结构相似区域,但相互之间也存在较大差异,如不同的后修饰反应等。我们以安丝菌素和萘霉素为研究材料,正在开展安莎类抗生素的合成后修饰机理及其在组合生物合成中的应用、安莎环的环化与释放、复杂的生物合成调控机制等研究。
3、次生代谢产物生物合成基因资源挖掘
充分利用我国丰富的微生物资源和基因簇克隆的大量成果,通过关键结构基团合成基因保守区设计兼并性引物,通量筛选可能的次生代谢生物合成基因簇,然后以此为指导寻找目标化合物,建立化合物和合成基因资源库。
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成果数
4
白林泉, Kazuyuki Minagawa, [a] Yirong Zhang, [b] Takuya Ito, [a] Linquan Bai, *[b] Zixin Deng, [b] and Taifo Mahmud*[a]
ChemBioChem 2007, 8, 632-641,-0001,():
-1年11月30日
The gene valC,which encodes an enzyme homologous to the 2-epi-5-epi-valiolone kinase (AcbM) of the acarbose biosynthetic pathway,was identified in the validamycin A biosynthetic gene cluster. Inactivation of valC resulted in mutants that lack the ability to produce validamycin A. Complementation experiments with a replicating plasmid harboring full-length valC restored the production of validamycin A,thus suggesting a critical function of valC in validamycin biosynthesis. In vitro characterization of ValC revealed a new type of C7-cyclitol kinase,which phosphorylates valienone and validone—but not 2-epi-5-epi-valiolone,5-epi-valiolone, or glucose—to afford their 7-phosphate derivatives. The results provide new insights into the activity of this enzyme and also confirm the existence of two different pathways leading to the same end-product: the valienamine moiety common to acarbose and validamycin A.
biosynthesis · cyclitols · kinases · valC · validamycin
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【期刊论文】Antibiotic biosynthetic pathways and pathway engineering-a growing research field in China†
白林泉, Zixin Deng* and Linquan Bai*
Nat. Prod. Rep., 2006, 23, 811-827,-0001,():
-1年11月30日
This review describes the recent research activities in China in relation to studies on antibiotic biosynthetic pathways and pathway engineering in actinomycetes. 75 references are cited.
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白林泉, Linquan Bai, Lei Li, , Hui Xu, Kazuyuki Minagawa, Yi Yu, Yirong Zhang, Xiufen Zhou, Heinz G. Floss, Taifo Mahmud, * and Zixin Deng, *
Chemistry & Biology 13, 387-397,-0001,():
-1年11月30日
A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VALA) 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.
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白林泉, Yi Yu, Linquan Bai, Kazuyuki Minagawa, Xiaohong Jian, Lei Li, Jialiang Li, Shuangya Chen, Erhu Cao, Taifo Mahmud, Heinz G. Floss, Xiufen Zhou, and Zixin Deng*
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Sept. 2005, p. 5066-5076,-0001,():
-1年11月30日
gene cluster responsible for the biosynthesis of validamycin, an aminocyclitol antibiotic widely used as a control agent for sheath blight disease of rice plants, was identified from Streptomyces hygroscopicus subsp. jinggangensis 5008 using heterologous probe acbC, a gene involved in the cyclization of D-sedoheptulose 7-phosphate to 2-epi-5-epi-valiolone of the acarbose biosynthetic gene cluster originated from Actinoplanes sp. strain SE50/110. Deletion of a 30-kb DNA fragment from this cluster in the chromosome resulted in loss of validamycin production, confirming a direct involvement of the gene cluster in the biosynthesis of this important plant protectant. A sequenced 6-kb fragment contained valA (an acbC homologue encoding a putative cyclase) as well as two additional complete open reading frames (valB and valC, encoding a putative adenyltransferase and a kinase, respectively), which are organized as an operon. The function of ValA was genetically demonstrated to be essential for validamycin production and biochemically shown to be responsible specifically for the cyclization of D-sedoheptulose 7-phosphate to 2-epi-5-epi-valiolone in vitro using the ValA protein heterologously overexpressed in E. coli. The information obtained should pave the way for further detailed analysis of the complete biosynthetic pathway, which would lead to a complete understanding of validamycin biosynthesis.
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