Text Size

Li, Tsung-Lin 李宗璘

LiTL_6x7副研究員


Email: tlli@gate.sinica.edu.tw
Telephone: 02-27871235
[ CV ]



EDUCATION AND POSITIONS HELD:

  • Ph.D., Chemistry, University of Cambridge (UK), 2004
  • Specialist, National Quarantine Service, Department of Health, Executive Yuan, Taipei, Taiwan, 1991.6-1991.12
  • Specialist, Chemistry Division, National Laboratories of Foods & Drugs, Department of Health, Executive Yuan, Taipei, Taiwan, 1991-1995
  • Teaching assistant, Food Science & Technology, The Ohio State University, 1995-1997
  • Specialist, Microbiology Division, National Laboratories of Foods and Drugs, Department of Health, Executive Yuan, Taipei, Taiwan, 1998-2000
  • Associate Research Scientist, University of Cambridge, 2003-2004
  • Postdoctoral Fellow, Genomics Research Center, 2004-2004
  • Assistant Professor, Biotechnology, Food Science, National Taiwan Ocean University, 2004-2007
  • Assistant Research Fellow, Genomics Research Center, Academia Sinica, 2007-2011
  • Adjunct Assistant/Associate Professor, Biotechnology Center, National Chung Hsing University, 2009-present
  • Adjunct Assistant/Associate Professor, Marine Biotechnology Center, National Sun Yat-sen University, 2010-present
  • Associate Research Fellow, Genomics Research Center, Academia Sinica, 2011-present 

HONORS:

  • National Certificate, Professionals and Technologists in Nutrition, 1991
  • National Certificate, National Senior Civil Service Examination (Environmental Hygiene), 1991
  • EPA Certificates, Environmental Toxicology (EPA, Taiwan), 1994
  • Annual Research Award (Department of Health), 1996
  • National Annual Research Award (Executive Yuan), 1997
  • National Certificate, National Advanced Senior Civil Service Examination (Hygiene Analysis), 1998
  • Overseas PhD Fellowship, Ministry of Education (Medical Chemistry), 1998

RESEARCH INTERESTS:

Natural product chemistry

Research in the Li lab encompasses a broad spectrum of natural product chemistry in particular in the scopes of elucidation and manipulation of biosynthetic pathways to vital natural products. Natural product chemistry had its genesis in the study of naturally occurring substances, and this remains intellectual challenge and certainly a constant source of information. Current targets include glycopeptides (mannopeptimycin, enduracidine, A40926, teicoplanin, chloroeremomycin), aminoglycosides (moenomycin, minosaminomycin), and marine toxin (tetrodotoxin).

Microbial pathogenicity

The lab is also involved in a multidisciplinary study for characterizing mechanisms of microbial pathogenicity. The current targeted microbe is Klebsiella pneaumoniae K1, which is the major causative bacterium of hospital-acquired, debilitated and immuno-compromised infections in Taiwan. Its complete genome has been sequenced recently. The overall goal of the program project is to understand the relationship between virulence, CPS (capsular polysaccharide) structure, and biosynthesis of the CPS.

Current Research Targe

Current Research Target

Proposed CPS assembly machinery

Proposed CPS assembly machinery

 

我們的研究工作主要著重於天然產物化學,特別是對於天然產物生合成路徑的闡釋及運用基因工程來發展更具生理效能的藥物。目前研究的重點天然產物包含:醣胜 肽類藥物(glycopeptides: mannopeptimycin, enduracidine, A40926, teicoplanin, chloroeremomycin), 氨基糖類藥物(aminoglycosides: moenomycin, minosaminomycin)及海洋毒素(marine toxins: tetrodotoxin)等。此外,我們也參與探討微生物致病性的群體研究,目前研究重點是針對一株對台灣公共衛生造成潛在威脅的克雷伯氏菌—K1 (Klebsiella Pneumoniae K1),我們正進行此菌表面多醣體分子的成份與結構分析,及其獨特表面多醣體分子的生合成機制與侵入宿主所引發免疫反應等的研究,期以建構克雷伯氏菌的致病模型。

RESEARCH HIGHLIGHTS:

Li-TL-Research_highlight
             Interception of teicoplanin oxidation intermediates yields new antimicrobial scaffolds

 

  1. Overcoming resistance (The Scientist)
  2. Dbv29 translation (SciBX) 
  3. Building a better germ-killer (A-IMBN) 
  4. 抗生素興亡史 (科學人第112期2011年6月號) 
  5. 李宗璘博士研究團隊以調整酵素方式成功增強現有抗生素藥效 (中央研究院 院新聞稿) 
  6. 巧手調整酵素,李宗璘實驗室以綠化學解除抗藥性窘境 (中央研究院基因體研究中心 新聞) 
  7. 醣胜肽類抗生素生合成酵素之探討 (中央研究院 週報第1125期 知識天地) 
  8. 功能基因體研究群發現關鍵酵素,可解決抗生素失效困境 (中央研究院基因體研究中心 新聞)

SELECTED PUBLICATIONS:

  • K. C. Wang, S. Y. Lyu, Y. C. Liu, C. Y. Chang, C. J. Wu & T. L. Li*, accepted, “Insights into the binding specificity and catalytic mechanism of N-acetylhexosamine 1-phosphate kinases through multiple-reaction complexes”, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY. (SCI)
  • X. W. Zou, Y. C. Liu, N. S. Hsu, C. J. Huang, S. Y. Lyu, H. C. Chan, C. Y. Chang, H. W. Yeh, K. H. Lin, C. J. Wu, M. D. Tsai, T. L. Li*, accepted, “Structure and mechanism of a non-heme iron-SAM dependent C-methyltransferase and its engineering to hydratase and O-methyltransferase”, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY. (SCI)
  • C. Y. Chang, S. Y. Lyu, Y. C. Liu, N. S. Hsu, C. C. Wu, C. F. Tang, K. H. Lin, J. Y. Ho, C. J. Wu, M. D. Tsai, T. L. Li*, 2014, “Biosynthesis of Streptolidine Involved Two Unexpected Intermediates Produced by a Dihydroxylase and a Cyclase through Unusual Mechanisms”, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 53, 1943-1948. (SCI)
  • H. C. Wu, Y. S. Li, Y. C. Liu, S. Y. Lyu, C. J. Wu, T. L. Li*, 2012, “Chain elongation and cyclization in type III PKS DpgA”, CHEMBIOCHEM, 13(6), 862-871. (SCI)
  • T. L. Li*, Y. C. Liu, S. Y. Lyu, 2012, “Combining biocatalysis and chemoselective chemistries for glycopeptide antibiotics modification”, CURRENT OPINION IN CHEMICAL BIOLOGY, 16, 170-178. (SCI)
  • S. H. Chen, D. R. Hwang, G. H. Chen, N. S. Hsu, Y. T. Wu, T. L. Li*, C. H. Wong*, 2012, “Engineering transaldolase in Pichia stipitis to improve bioethanol production”, ACS CHEMICAL BIOLOGY, 7(3), 481-486. (SCI)
  • J. Y. Ho, T. L. Lin, A. Lee, A. N. Cheng, C. Y. Li, M. C. Chen, S. H. Wu, J. T. Wang*, T. L. Li*, M. D. Tsai*, 2011, “Functions of some capsular polysaccharide biosynthetic genes in Klebsiella pneumoniae NTUH K-2044”, PLOS ONE, 6(7), e21664. (SCI)
  • Y. C. Liu, Y. S. Li, S. Y. Lyu, L. J. Hsu, Y. H. Chen, Y. T. Huang, H. C. Chan, C. J. Huang, G. H. Chen, C. C. Chou, M. D. Tsai, T. L. Li*, 2011, “Interception of teicoplanin oxidation intermediates yields new antimicrobial scaffolds”, NATURE CHEMICAL BIOLOGY, 7, 304-309. (SCI)
  • H. C. Chan, Y. T. Huang, S. Y. Lyu, C. J. Huang, Y. S. Li, Y. C. Liu, C. C. Chou, M. D. Tsai, and T. L. Li*, 2011, “Regioselective deacetylation based on teicoplanin-complexed Orf2* crystal structures”, MOLECULAR BIOSYSTEMS, 7(4), 1224-1231. (SCI)
  • Y. T. Huang, S. Y. Lyu, P. H. Chuang, N. S. Hsu, Y. S. Li, H. C. Chan, C. J. Huang, Y. C. Liu, C. J. Wu, W. B. Yang, T. L. Li*, 2009, “In vitro characterization of enzymes involved in the synthesis of nonproteinogenic residue (2S,3S)-b-methylphenylalanine in glycopeptide antibiotic mannopeptimycin”, CHEMBIOCHEM, 10, 2480-2487. (SCI)
  • T. L. Li*, D. Spiteller, J. B. Spencer, 2009, “Identification of a pentaketide stilbene produced by a type III polyketide synthase from Pinus sylvestris and characterisation of free coenzyme A intermediates”, CHEMBIOCHEM, 10, 896-901. (SCI)
  • Y. S. Li, J. Y. Ho, C. C. Huang, S. Y. Lyu, C. Y. Lee, Y. T. Huang, C. J. Wu, H. C. Chan, C. J. Huang, N. S. Hsu, M. D. Tsai and T. L. Li*, 2007, “A unique flavin mononucleotide-linked primary alcohol oxidase for glycopeptide A40926 maturation”, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 129, 13384-13385. (SCI)
  • J. Y. Ho, Y. T. Huang, C. J. Wu, Y. S. Li, M. D. Tsai and T. L. Li*, 2006, “Glycopeptide Biosynthesis: Dbv21/Orf2* from dbv/tcp Gene Clusters Are N-Ac-Glm Teicoplanin Pseudoaglycone Deacetylases and Orf15 from cep Gene Cluster Is a Glc-1-P Thymidyltransferase”, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 128(42), 13694-13695. (SCI)
  • F. Huang, S. F. Haydock, D. Spiteller, T. Mironenko, T. L. Li, P. F. Leadlay, D. O'Hagan and J. B. Spencer*, 2006, “The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya: a thioesterase confers resistance to fluoroacetyl-coenzyme A.”, CHEMISTRY & BIOLOGY, 13(5), 475-484. (SCI)
  • T. L. Li, F. Huang, S. F. Haydock*, T. Mironenko, P. F. Leadlay and J. B. Spencer*, 2004, “Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase”, CHEMISTRY & BIOLOGY, 11(1), 107-119. (SCI)
  • T. L. Li*, Y. J. Chung-Wang and Y. C. Shih, 2002, “Determination and confirmation of chloramphenicol residues in swine muscle and liver”, JOURNAL OF FOOD SCIENCE, 67(1), 21-28. (SCI)
  • T. L. Li, O. W. Choroba, H. Hong, D. H. Williams and J. B. Spencer*, 2001, “Biosynthesis of the vancomycin group of antibiotics: characterisation of a type III polyketide synthase in the pathway to (S)-3,5-dihydroxyphenylglycine”, CHEMICAL COMMUNICATIONS, 20, 2156-2157. (SCI)
  • T. L. Li, O. W. Choroba, E. H. Charles, A. M. Sandercock, D. H. Williams and J. B. Spencer*, 2001, “Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of two unusual amino acids occurring in the vancomycin group of antibiotics”, CHEMICAL COMMUNICATIONS, -18, 1752-1753. (SCI)