研究員 / 化學生物學組執行長

tlli
02-27871235

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 Professor, 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 Professor, Genomics Research Center, Academia Sinica, 2011-2019
• Professor, Genomics Research Center, Academia Sinica, 2019-present
• Deputy Director, Genomics Research Center, Academia Sinica, 2019-2023
• Division Director of Chemical Biology, GRC, Academia Sinica, Taiwan, 2023-present

HONORS:

• NSTC Outstanding Research Award, 2023
• Investigator Award (Academia Sinica), 2020-2024
• Career Development Award (Academia Sinica), 2014-2018
• Career Development Award (National Health Research Institutes), 2012-2015
• Academia Sinica Significant Research, 2018
• Academia Sinica Significant Research, 2014
• Academia Sinica Significant Research, 2011
• Academia Sinica Major Discovery, 2007
• Overseas PhD Fellowship (in Chemistry, Ministry of Education, MOE), 1998
• National Certificate in Hygiene Analysis, Advanced National Senior Civil Service Examination (Examination Yuan), 1998
• Researcher Award, National Annual Research Award (Executive Yuan), 1997
• Researcher Award, Annual Research Award (Department of Health), 1996
• National Certificate in Environmental Hygiene, National Senior Civil Service Examination (Examination Yuan), 1991
• National Certificate in Dietician Profession (Department of Health), 1991
• National Certificate in Nutrition, Professionals and Technologists Examination (Examination Yuan), 1991

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.

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:

N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry

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)
9. 轉酮酶解密 發現前所未見的雙自由基中間體 (中央研究院基因體研究中心 新聞)
10. 大自然為師 解鎖酵素StnK3翻轉生物合成路徑 (中央研究院基因體研究中心 新聞)
11. 首揭酵素利用蛋白質與受質間氮氧硫鍵橋化學–氨基糖苷類抗生素逆轉勝 (中央研究院基因體研究中心 新聞)

SELECTED PUBLICATIONS:

• S. P. Selvaraj, K. H. Lin, W. C. Lin, M. F. You, T. L. Li*, J. Y Chen*, 2024, “Rejuvenation of Meropenem by Conjugation with Tilapia Piscidin-4 Peptide Targeting NDM-1 Escherichia coli”, ACS OMEGA, 28;9(27):29756-29764. (SCIE)
• Y. L. Wang, C. Y. Chang, N. S. Hsu, I. W. Lo, K. H. Lin, C. L. Chen, C. F. Chang, Z. C. Wang, Y. Ogasawara, T. Dairi, C. Maruyama, Y. Hamano*, T. L. Li*, 2023, “N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry”, NATURE COMMUNICATIONS, 14:2528, 1-14. (SCIE)
• I. W. Lo, G. Y. Liao, J. C. Lee, C. I. Chang, Y. C. Wu, S. P. Liu, H. J. Su, C. I. Liu, C. Y. Kuo, Z.Y. Lin, T. L. Li*, Y. S. Lin*, C. C. Liaw*, 2022, “Novel Aporphine- and Proaporphine-Clerodane Hybrids Identified from the Barks of Taiwanese Polyalthia Longifolia var. pendula with Strong Anti-DENV2 Activity”, PHARMACEUTICS, 15(10), 1218, 1-15. (SCIE)
• Z. C. Wang, I. W. Lo, K. H. Lin, A. N. Cheng, S. M. Zadeh, Y. H. Huang, T. L. Li*, 2022, “Genetic and biochemical characterization of halogenation and drug-transportation genes encoded in the albofungin biosynthetic gene cluster”, APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 88(17):e0080622, 1-20. (SCIE)
• E. Astani, S. M. Zadeh, N. S. Hsu, K. H. Lin, S. Sardari, T. L. Li*, 2022, “Intermolecular Interactions of Nucleoside Antibiotic Tunicamycin with On-Target MraYcb-TUN and Off-Target DPAGT1-TUN in the Active Sites Delineated by Quantum Mechanics/Molecular Mechanics Calculations”, ACS OMEGA, 7(37), 32970-32987. (SCIE)
• S. M. Zadeh, M. H. Chen, Z. C. Wang, E. K. Astani, I. W. Lo, K. H. Lin, N. S. Hsu, K. Adhikari, S. Y. Lyu, H. Y. Tsai, Y. Terasawa, M. Yabe, K. Yamamoto, S. Ichikawa, T. L. Li*, 2022, “β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin”, COMMUNICATIONS CHEMISTRY, 5, 87, 1-16. (SCIE)
• C. C. Liaw, I. W. Lo, Y. C. Lin, H. T. Huang, L. J. Zhang, P. C. Hsiao, T. L. Li,* Y. H. Kuo*, 2022, “Four cucurbitane glycosides taimordisins A–D with novel furopyranone skeletons isolated from the fruits of Momordica charantia”, FOOD CHEMISTRY: X, 14, 100286. (SCIE)
• R. Rattinam, R. S. Basha, Y. L. Wang, Z. C. Wang, N. S. Hsu, K. H. Lin, S. Malek Zadeh, K. Adhikari, J. P. Lin, T. L. Li*, 2022, “KasQ an epimerase primes the biosynthesis of aminoglycoside antibiotic kasugamycin and KasF/H acetyltransferases inactivate its activity”, BIOMEDICINES, 10(2), 212. (SCIE)
• M. H. Chen, Y. S. Li, N. S. Hsu, K. H. Lin, Y. L. Wang, Z. C. Wang, C. F. Chang, J. P. Lin, C. Y. Chang, T. L. Li*, 2022, “Structural and mechanistic bases for StnK3 and its mutants-mediated Lewis-acid-dependent epimerization and retro aldol reactions”, ACS CATALYSIS, 12, 1945-1956. (SCIE)
• S. Malek Zadeh, E. Astani, Z. C. Wang, K. Adhikari, R. Rattinam, T. L. Li*, 2020, “Theoretical study of intermolecular interactions between critical residues of membrane protein MraYAA and Promising Antibiotic Muraymycin D2”, ACS OMEGA, 5(36), 22739–22749. (SCIE)
• K. Adhikari, I. W. Lo, C. L. Chen, Y. L. Wang, K. H. Lin, S. Malek Zadeh, R. Rattinam, Y. S. Li, C. J. Wu, T. L. Li*, 2020, “Chemoenzymatic synthesis and biological evaluation for bioactive molecules derived from bacterial benzoyl coenzyme A ligase and plant type III polyketide synthase”, BIOMOLECULES, 10(5), 738. (SCIE)
• K. H. Lin, S. Y. Lyu, H. W. Yeh, Y. S. Li, N. S. Hsu, C. M. Huang, Y. L. Wang, H. W. Shih, Z. C. Wang, C. J. Wu, T. L. Li*, 2020, “Structural and chemical trapping of short-lived flavin-oxide intermediates reveals substrate-directed reaction multiplicity”, PROTEIN SCIENCE, 29, 1655-1666. (SCIE)
• S. Y. Lyu, K. H. Lin, H. W. Yeh, Y. S. Li, C. M. Huang, Y. L. Wang, H. W. Shih, N. S. Hsu, C. J. Wu, T. L. Li*, 2019, “The flavin mononucleotide cofactor in α-hydroxyacid oxidases exerts its electrophilic/nucleophilic duality in control of the substrate oxidation level”, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 75(10), 918-929.
• H. W. Yeh, K. H. Lin, S. Y. Lyu, Y. S. Li, C. M. Huang, Y. L. Wang, H. W. Shih, N. S. Hsu, C. J. Wu, T. L. Li*, 2019, “Biochemical and structural explorations for alpha-hydroxyacid oxidases reveal a 4-electron oxidative decarboxylation reaction”, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 75(Pt 8), 733–742.
• C. M. Huang, S. Y. Lyu, K. H. Lin, C. L. Chen, M. H. Chen, H. W. Shih, N. H. Hsu, I. W. Lo, Y. L. Wang, Y. S. Li, C. J. Wu, T. L. Li*, 2019, “Teicoplanin reprogrammed with the N-Acyl-glucosamine pharmacophore at the penultimate residue of aglycone acquires broad-spectrum antimicrobial activities effectively killing gram-positive and -negative pathogens”, ACS INFECTIOUS DISEASES, 5(3), 430-442. (SCIE)
• N. S. Hsu, Y. L. Wang, K. H. Lin, C. F. Chang, S. C. Ke, S. Y. Lyu, L. J. Hsu, Y. S. Li, S. C. Chen, K. C. Wang, T. L. Li*, 2018, “Evidence of diradicals involved in the yeast transketolase catalyzed keto-transferring reactions”, CHEMBIOCHEM, 19(22), 2395-2402. (SCIE)
• N. S. Hsu, Y. L. Wang, K. H. Lin, C. F. Chang, S. Y. Lyu, L. J. Hsu, Y. C. Liu, C. Y. Chang, C. J. Wu, T. L. Li*, 2018, “The mesomeric effect of thiazolium on non-Kekule diradicals in Pichia stipitis transketolase”, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 57(7), 1802-1807. (SCIE)
• L. J. Hsu, N. S. Hsu, Y. L. Wang, C. J. Wu, T. L. Li*, 2016, “Structural and biochemical interrogation on transketolase from Pichia stipitis for new functionality”, PROTEIN ENGINEERING DESIGN & SELECTION, 29(11), 513-522. (SCIE)
• S. Y. Lyu, Y. C. Liu, C. Y. Chang, C. J. Huang, Y. H. Chiu, C. M. Huang, N. S. Hsu, K. H. Lin, C. J. Wu, M. D. Tsai, T. L. Li*, 2014, “Multiple complexes of long aliphatic N-acyltransferases lead to synthesis of 2,6-diacylated/2-acyl-substituted glycopeptide antibiotics effectively killing vancomycin-resistant Enterococcus”, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 136(31), 10989-10995. (SCIE)
• 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*, 2014, “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, 70(6), 1549-1560.
• K. C. Wang, S. Y. Lyu, Y. C. Liu, C. Y. Chang, C. J. Wu, T. L. Li*, 2014, “Insights into the binding specificity and catalytic mechanism of N-acetylhexosamine 1-phosphate kinases through multiple-reaction complexes”, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 70(5), 1401-1410.
• 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(7), 1943-1948. (SCIE)
• 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. (SCIE)
• 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. (SCIE)
• 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. (SCIE)
• 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. (SCIE)
• 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. (SCIE)
• 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 OMICS (MOLECULAR BIOSYSTEMS), 7(4), 1224-1231.
• 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. (SCIE)
• 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. (SCIE)
• 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. (SCIE)
• 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. (SCIE)
• 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”, CELL CHEMICAL BIOLOGY (CHEMISTRY & BIOLOGY), 11(1), 107-119.
• 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. (SCIE)
• 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. (SCIE)
• 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. (SCIE)
• T. L. Li, J. M. King and Y. B. Min*, 2000, “Quenching mechanisms and kinetics of carotenoids in riboflavin photosensitized singlet oxygen oxidation of vitamin D-2”, JOURNAL OF FOOD BIOCHEMISTRY, 24 (6), 477-492. (SCIE)
• T. L. Li* and D. B. Min*, 1998, “Stability and photochemistry of vitamin D-2 in model system”, JOURNAL OF FOOD SCIENCE, 63 (3), 413-417. (SCIE)
• W. C. Lee, T. L. Li*, W. J. Cheng, P. C. Chang and S. S. Chou, 1998, “Survey of nicotine and tar yields of domestic and imported cigarettes”, JOURNAL OF FOOD AND DRUG ANALYSIS, 6 (4), 691-701. (SCIE)