南京大学校友谢新凯《化学和生物学》杂志文章

　　生物通报道：在2006年11月的《化学和生物学》杂志上刊登了加州大学洛杉矶分校的唐毅（Yi Tang）教授研究组发表的一篇有关降血脂药物洛伐他汀（ lovastatin ）类似物生物合成研究的新文章。该文章的第一作者是华人研究生谢新凯（Xinkai Xie），他在南京大学获得学士学位并于2005年在南京大学获得硕士学位。  

天然产物lovastatin和它的半合成物——更有效的衍生物simvastatin都是治疗血胆脂醇过多症的重要药物。在这项研究中，研究人员报道了lovastatin生物合成途径中的一种酰基转移酶LovD的生化特征。

  他们证实，LovD对酰基运载体、酰基地物和decalin酰基受体的特异性较宽。LovD能够有效地催化从辅酶A 硫酯或SNAC 硫酯到monacolin J的酰基转移。当α-dimethylbutyryl-SNAC被作为酰基供体时，LovD能够将monacolin J和6-hydroxyl-6-desmethylmonacolin J分别转化成simvastatin和huvastatin。  

利用大肠杆菌的LovD过表达株作为生物催化剂，通过一种单独的发酵步骤能够合成一定量的simvastatin。  

这些研究结果证实LovD是一种可操作的药用重要降胆固醇药物的生物合成的一种很有潜力的酶。

Xinkai’s favorite toy

 

 

2006高等学校科学技术奖授奖项目（生物类I）

2006高等学校科学技术奖授奖项目（生物类II） 

2006高等学校科学技术奖授奖项目（生物类III）

 

唐毅教授

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唐毅教授

 

唐毅教授简介：

Education

B.S. 1997 Pennsylvania State University
Ph.D. 2002 California Institute of Technology

 

唐毅教授研究组2001年－2005年发表的研究论文目录

 

PUBLICATIONS (*: equal contribution authors)

 

22. Zhang, W., Watanabe, K., Wang, C. C. C., Tang, Y. “Heterologous Biosynthesis of Amidated Polyketides with Novel Cyclization Regioselectivity from Oxytetracycline Polyketide Synthase” J. Nat. Prod. 2006, 69, 1633-1636. Link

21. Xie, X., Watanabe, K., Wojcicji, W. A., Wang, C. C. C., Tang, Y. “Biosynthesis of lovastatin analogs with a broadly specific acyltransferase.” Chem. Biol. 2006, 13, 1161-1169. Link

20. Zhang, W., Ferreira, J. P., Tang, Y. "Regulation of Secondary Metabolism Biosynthesis." In: Smolke, C.D., ed. Handbook for Metabolic Pathway Engineering. CRC Press. 2006 Submitted.

19. Tang, Y.; Ma, S.M; Wojicicki, W. A. "Applications of Metabolic Engineering for Natural Drug Discovery." In: Smolke, C.D., ed. Handbook for Metabolic Pathway Engineering. CRC Press. 2006 Submitted.

18. Zhang, W., Ames, B., Tsai, S-C., Tang, Y., "Tetracycline Biosynthesis: Sequencing of the Oxytetracycline Gene Cluster and Reconstitution of the Malonamyl-Specific Initiation module." Appl. Environ. Microb.. 2006, 72, 2573-2580.  pdf

17. Zhang, W., Tang, Y., "Engineering Starter Units in Aromatic Polyketides." In ACS Volume Based on Polyketides: Biosynthesis, Biological Activity and Genetic Engineering. eds S. R. Baerson; American Chemical Society, 2006.

16. Tang, Y., Khosla, C., "Diversity from Mother Nature: natural and unnatural products." In Exploiting Chemical Diversity for Drug Discovery, eds P. Bartlett and M. Entzeroth; Royal Society of Chemistry, 2006. Link

15. Lee. T. S.*, Khosla, C., Tang, Y.* "Orthogonal Protein Interactions in Spore Pigment Producing and Antibiotic Producing Type II Polyketide Synthases." J. Antibiotics, 2005, 58, 664-667.

14. Lee. T. S.*, Khosla, C., Tang, Y.* "Engineered Biosynthesis of Aklanonic Acid Analogs." J. Am. Chem. Soc., 2005, 127, 12254-12262.

13. Khosla, C., Tang, Y., "Chemistry. A new route to designer antibiotics." Science 2005, 308, 367-368.

12. Tang, Y., Koppisch, A., Khosla, C. "The Acyltransferase Homolog Found in Initiation Modules of Type II PKS is an Acetyl-ACP Thiolase that Suppresses Acetate-Priming of the KS-CLF." Biochemistry 2004, 43, 9546-9555.

11. Tang, Y., Lee, T. S., Lee, H. Y., Khosla, C. "Exploring the Biosynthetic Potential of Bimodular Aromatic Polyketide Synthases." Tetrahedron, 2004, 7659-7671.

10. Kumar, P.*, Khosla, C., Tang, Y.* "Manipulation and Analysis of Polyketide Synthases." Methods in Enzymology Volume 388: Protein Engineering 2004, 269-293.

9. Tang, Y., Lee, T. S., Khosla, C. "Engineered Biosynthesis of Regioselectively Modified
Aromatic Polyketides Using Bimodular Polyketide Synthases." PLoS Biol. 2004, 2, 227-237.

8. Tang, Y., Tsai, S. C., Khosla, C. "Polyketide Chain Length Control by Chain Length Factor." J. Am. Chem. Soc. 2003, 125, 12708-12709.

7. Tang, Y., Lee, T. S., Kobayashi, S., Khosla, C. "Ketosynthases in the Initiation and Elongation Modules of Aromatic Polyketide Synthases Have Orthogonal Acyl-Carrier Protein Specificity." Biochemistry 2003, 42, 6588-6595.

6. Cirino, P.C , Tang, Y., Takahashi, K., Tirrell, D. A., Arnold, F. H. "Global Incorporation of Norleucine in Place of Methionine in Cytochrome P450 BM-3 Heme Domain Increases Peroxygenase Activity." Biotechnol Bioeng. 2003 20, 729-734.

5. Wang, P., Tang, Y., Tirrell, D. A., "Incorporation of Trifluoroisoleucine into Proteins In Vivo." J. Am. Chem. Soc. 2003, 125, 6900-6906.

4. Tang, Y., Tirrell, D. A. "Attenuation of Leucyl-tRNA Synthetase Proofreading Activity in Escherichia coli Allows Introduction of An Array of Unnatural Amino Acids in vivo." Biochemistry 2002, 41, 10635-10645.

3. Tang, Y., Tirrell, D. A. "Biosynthesis of Highly Stable Coiled-coils Containing Hexafluoroleucine Using an Engineered Bacterial Host." J. Am. Chem. Soc. 2001, 123, 11089-11090.

2. Tang, Y., Ghirlanda, G., Petka, W. A., Nakajima, T., W. A., DeGrado, W. F., Tirrell, D. A. "Fluorinated Coiled-coils Prepared in vivo Display Enhanced Thermal and Chemical Stability." Angew. Chem. Int. Ed. 2001, 40, 1494-1497.

1. Tang, Y., Ghirlanda, G., Vaidehi, N., Kua, J., Mainz, D. T., Goddard, W. A., DeGrado, W. F., Tirrell, D. A. "Stabilization of Leucine Zipper Coiled-coils using Trifluoroleucine." Biochemistry 2001, 40, 2790-2796.