林雙君

林雙君，男，上海交通大學生命科學技術學院，特別研究員，教授。

基本介紹

• 中文名：林雙君
• 國籍：中國
• 職業：曾任威斯康星大學麥迪遜分校藥學院研究助理
• 畢業院校：中國科學院上海藥物研究所

個人簡歷

2002年7月畢業於中國科學院化學所，從事生物轉化和生物催化研究，獲有機化學博士學位。 2002年12月至2005年8月在加拿大的埃爾伯塔大學化學系從事博士後研究，主要從事糖轉移酶的生化表征和糖轉移酶在寡糖合成中的套用，以及寡糖的化學合成。2005年9月任威斯康星大學麥迪遜分校藥學院研究助理，主要從事烯二炔類抗生素的生物合成研究。於2008年9月回國，受聘於上海交通大學任特別研究員，現任職於上海交通大學微生物代謝教育部重點實驗室。共發表21篇SCI研究論文，其中JACS 3篇、 PNAS 2篇、Nature Structural & Molecular Biology 1 篇，以及有機化學專業雜誌JOC 2篇。

研究方向

1. 抗菌和抗腫瘤的微生物次級代謝產物的生物合成和組合生物合成

微生物次代謝物是由微生物產生的天然產物，通常結構複雜、活性官能團較多。這些天然產物的合成通常是以小分子為原料，經過一系列連續的酶催化反應組裝合成的。通過克隆負責目標天然產物的生物合成基因簇，闡明天然產物在生物體內的生物合成途徑，闡述酶催化反應的機理。再通過對目標天然產物合成途徑中的合成基因或調控基因做合理的修飾，以期產生結構類似的“非天然”的天然產物，豐富可供生理活性化合物篩選的物質基礎。

2. 微生物來源的生理活性天然產物的篩選和鑑定

自20世紀20年代末青黴素的發現至今，微生物仍然是藥物和藥物先導化合物的重要來源。基於極端環境微生物包括深海微生物、嗜熱、嗜鹽、嗜壓微生物以及共生微生物產生的結構新穎的化合物的高几率，套用主要疾病如腫瘤、心血管疾病、糖尿病和感染性疾病作為靶標，對微生物的代謝物進行篩選、分離純化和結構鑑定。

3. 酶作為生物催化劑在有機合成中的套用

酶作為重要的生物催化劑，具有優異的化學選擇性、區域選擇性和立體選擇性。在理解生物合成途徑中催化天然產物生物合成的酶的催化機理的基礎上，拓展酶催化在有機合成中的套用，豐富有機合成方法學的研究。

發表論文

主要代表性論文：

1. 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.

2. 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.

3. 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.

4. 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)

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. Lin SJ, Tan CH, Jiang SH, Li YM and Zhu DY*, “C9-iridoids from Scrophularia buergeriana” Helvetica Chimica Acta 2006, 89, 2789-2793.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. Lin SJ, Jiang SH, Li YM, Zeng JF and Zhu DY*, “Two novel iridoids from Scrophularia buergeriana” Tetradron Letters 2000, 41, 1069-1071.

20. 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.

21. 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。