林双君 - 上海交通大学 - 生命科学技术学院

个人简介

1996年7月毕业于吉林大学化学系，获学士学位。1999年7月毕业于中国科学院上海药物研究所，从事天然产物分离纯化和结构鉴定，获有机化学硕士学位。2002年7月毕业于中国科学院化学所，从事生物转化和生物催化研究，获有机化学博士学位。 2002年12月至2005年8月在加拿大的埃尔伯塔大学化学系从事博士后研究，主要从事糖转移酶的生化表征和糖转移酶在寡糖合成中的应用，以及寡糖的化学合成。2005年9月任威斯康星大学麦迪逊分校药学院研究助理，主要从事烯二炔类抗生素的生物合成研究。于2008年9月回国，受聘于上海交通大学任特别研究员，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21篇SCI研究论文，其中JACS 3篇、 PNAS 2篇、Nature Structural & Molecular Biology 1 篇，以及有机化学专业杂志JOC 2篇。

研究领域

1. 抗菌和抗肿瘤的微生物次级代谢产物的生物合成和组合生物合成微生物次代谢物是由微生物产生的天然产物，通常结构复杂、活性官能团较多。这些天然产物的合成通常是以小分子为原料，经过一系列连续的酶催化反应组装合成的。通过克隆负责目标天然产物的生物合成基因簇，阐明天然产物在生物体内的生物合成途径，阐述酶催化反应的机理。再通过对目标天然产物合成途径中的合成基因或调控基因做合理的修饰，以期产生结构类似的“非天然”的天然产物，丰富可供生理活性化合物筛选的物质基础。 2. 微生物来源的生理活性天然产物的筛选和鉴定自20世纪20年代末青霉素的发现至今，微生物仍然是药物和药物先导化合物的重要来源。基于极端环境微生物包括深海微生物、嗜热、嗜盐、嗜压微生物以及共生微生物产生的结构新颖的化合物的高几率，应用主要疾病如肿瘤、心血管疾病、糖尿病和感染性疾病作为靶标，对微生物的代谢物进行筛选、分离纯化和结构鉴定。 3. 酶作为生物催化剂在有机合成中的应用酶作为重要的生物催化剂，具有优异的化学选择性、区域选择性和立体选择性。在理解生物合成途径中催化天然产物生物合成的酶的催化机理的基础上，拓展酶催化在有机合成中的应用，丰富有机合成方法学的研究。

近期论文

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Lin SJ, Van Lanen SG and Shen B*, “A Free-Standing Condensation Enzyme Catalyzing Ester Bond Formation in C-1027 Biosynthesis”. Proc. Natl. Acad. Sci. U.S.A. 2009,106, 4183-4188. Lin SJ, Van Lanen SG and Shen B*, “Characterization of the Two-Component, FAD-Dependent Monooxygenase SgcC that Requires Carrier Protein-Tethered Substrates for the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027”. J. Am. Chem. Soc. 2008, 130, 6616-6623. Lin SJ, Van Lanen SG and Shen B*, “Regiospecific Chlorination of (S)--Tyrosyl-S-Carrier Protein Catalyzed by SgcC3 in the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027”. J. Am. Chem. Soc. 2007, 129, 12432-8. Van Lanen SG, Lin SJ and Shen B*, “The Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 Involves a New Branching Point in Chorismate Metabolism” Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 494-499.( Featured in C & E News, January 14, 2008, p36) Luo Y, Lin SJ, Zhang J, Cooke HA, Bruner SD and Shen B*, “Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor abtibiotic neocarzinastatin”. J. Biol. Chem. 2008, 283, 14694-14702. Van Lanen SG, Lin SJ, Dorrestein PC, Kelleher NL, Shen B*, “Substrate specificity of the adenylation enzyme SgcC1 involved in the biosynthesis of the enediyne antitumor antibiotic C-1027” J. Biol. Chem. 2006, 281, 29633-29640. Rose NL, Completo GC, Lin SJ, McNeil M, Palcic MM*, Lowary TL*. “Expression, Purification, and Characterization of a Galactofuranosyltransferase Involved in Mycobacterium tuberculosis Arabinogalactan Biosynthesis” J. Am. Chem. Soc. 2006, 128, 6721-6729. Greco A, Ho JGS, Lin SJ, Palcic MM, Rupnik M, Ng KKS*, “Carbohydrate Recognition by Clostridium difficile Toxin A” Nature Structural & Molecular Biology 2006, 13, 460-461. Ma B, Audette GF, Lin SJ, Palcic MM, Hazes B, and Taylor DE*, “Purification, kinetic characterization, and mapping of the minimal catalytic domain and the key polar groups of Helicobacter pylori alpha-(1,3/1,4)-fucosyltransferases” J. Biol. Chem. 2006, 281, 6385-6395. Lin SJ, Tan CH, Jiang SH, Li YM and Zhu DY*, “C9-iridoids from Scrophularia buergeriana” Helvetica Chimica Acta 2006, 89, 2789-2793. Bai Y, Lin SJ, Qi GZ, Palcic MM and Lowary TL*, “Synthesis of n-octyl 2,6-dideoxy-alpha-L-lyxo-hexopyranosyl-(1-2)-3-amino-3-deoxy--D-galacto-pyranoside, an analog of the H-disaccharide antigen” Carbohydrate Research 2006, 341, 1702-1707. Ridgway KM, Shi W, Lin SJ, Palcic MM and Lowary TL*, “Chemical and chemoenzymatic synthesis of a trisaccharide fragment of Tsukamurella paurometabola lipoarabinomannan”. Canadian Journal of Chemistry 2006, 84, 642-649. Wang MX*, Lin SJ, Liu J and Zheng QY. “Efficient biocatalytic synthesis of highly enantiopure -alkylated arylglycines and amides” Advanced Synthesis & Catalysis 2004,346, 439-445. Wang MX*, Lin SJ, Liu CS, Zheng QY and Li JS, “Nitrile biotransformations for highly efficient and enantioselective syntheses of electrophilic oxiranecarboxamides” J. Org. Chem. 2003, 68, 4570-4573. Wang MX* and Lin SJ “Practical and convenient enzymatic synthesis of enantio-pure alpha-amino acids and amides” J. Org. Chem. 2002, 67, 6542-6545. Wang MX* and Lin SJ, “Highly efficient and enantioselective synthesis of L-arylglycines and D-arylglycine amides from biotransformation of nitriles”. Tetrahedron Letters 2001, 42, 6925-6927. Guo L, Lin SJ, Yang YF, Qi L, Wang MX and Chen Y*, “Fast enantioseperation of aryglycine amides by capillary eletrophoresis with highly sulfated--cyclodextrin as a chiral selector”. Journal of Chromatography A 2003, 998 (1-2): 221-228. Guo L, Lin SJ, Dai DS, Yang YF, Qi L, Wang MX and Chen Y*, “Enantio-separation of -quaternary arylglycine amides by capillary electropherosis with human serum albumin” Analytical Letters 2003, 36 (7): 1451-1462. Lin SJ, Jiang SH, Li YM, Zeng JF and Zhu DY*, “Two novel iridoids from Scrophularia buergeriana” Tetradron Letters 2000, 41, 1069-1071. Dingle T, Wee S, Mulvey GL, Greco A, Kitova EN, Sun J, Lin SJ, Klassen JS, Palcic MM, Ng KK, Armstrong GD*, “Functional properties of the carboxy-terminal host cell-binding domains of the two toxins, TcdA and TcdB, expressed by Clostridium difficile”. Glycobiology 2008, 18, 698-706. Jiang SH, Wang HQ, Li YM, Lin SJ, Tan JJ, Zhu DY*. “Two new C18-norditerpenoid alkaloids from Aconitum delavayi” Chinese Chemical letters, 2007, 18, 409-411.