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个人简介

B.S. Tunghai University M.A. Columbia University M. Phil. Columbia University Ph.D. Columbia University NIEHS Postdoctoral Fellow, Massachusetts Institute of Technology Camille & Henry Dreyfus Grant for Distinguished New Faculty in Chemistry (1984) American Cancer Society Junior Faculty Research Award (1985) Eli Lilly Life Science Young Investigator Award (1985) NIH Research Career Development Award (1990-5) Horace S. Isbell Award, American Chemical Society, Division of Carbohydrate Chemistry (1993) National Institute of General Medical Sciences MERIT Award (1999) Distinguished McKnight University Professor, University of Minnesota (1999) Honorary Professor of Chemistry, University of Hong Kong (2001-2007) American Association for the Advancement of Science Fellow (2005) American Academy of Microbiology Fellow (2006) Japan Society for the Promotion of Science Fellow (2006) Nakanishi Prize, American Chemical Society, Division of Organic Chemistry (2007) Repligen Award in Chemistry of Biological Processes, American Chemical Society, Division of Biological Chemistry (2008) Elected Academician of Academia Sinica (2008) Tunghai University Distinguished Alumni Award (2008), Honorary Professor (2011) Honorary Professor, National Tsing Hua University, Taiwan (2011) A. I. Scott Medal for Excellence in Biological Chemistry Research (2011) American Chemical Society Fellow (2014) Arthur C. Cope Late Career Scholars Award, American Chemical Society (2014) Claude S. Hudson Award, American Chemical Society, Division of Carbohydrate Chemistry (2019) Norman R Farnsworth Research Achievement Award, The American Society of Pharmacognosy (2022)

研究领域

The major thrust of my research lies at the crossroads of chemistry and biology. My group is currently working on three general areas with the focus aimed at the elucidation of the mechanisms of novel enzymatic reactions and the design of methods to control and/or regulate their functions. Enzyme Mechanism and Inhibitor Design: Using a multi-faceted approach, we study the mechanisms of enzymes involved in diverse biological processes including the formation of bacterial cell wall, biosynthesis of and resistance to antibiotics, metabolism of lipids, and the posttranslational modification of nuclear proteins. A significant effort is devoted to the synthesis of compounds as mechanistic probes or specific inhibitors for these biological catalysts. Metabolic Pathway Engineering: Through selective disruption and/or substitution of sugar biosynthetic genes in the microorganisms which produce bioactive glycosylated secondary metabolites, we have demonstrated the feasibility of engineering nature’s biosynthetic machinery for the production of novel compounds carrying designed sugar appendages. Such a combinatorial biosynthetic approach bears a great promise of finding drugs with new or improved biological activity. Protein Function Regulation: We have recently initiated a study on poly(ADP-ribose) polymerase, an enzyme that recognizes damaged DNA and turns on the repairing machinery through polyADP-ribosylation of itself and other nuclear proteins. Such a posttranslational modification of proteins is also essential to other crucial cellular events including apoptosis.

近期论文

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Chen, Z.; Sato. S.; Geng. Y., Zhang, J.; Liu, H.-w. “Identification of the Early Steps in Herbicidin Biosynthesis Reveals an Atypical C-Glycosylation.” J. Am. Chem. Soc. 2022, 144, in press. De, B. C.; Zhang, W.; Yang, C.; Mándi, A.; Huang, C.; Zhang, L.; Liu, W.; Ruszczycky, M. W.; Zhu, Y.; Ma, M.; Bashiri, G.; Kurtán, T.; Liu, H.-w.; Changsheng Zhang, C. “Flavin-Enabled Reductive and Oxidative Epoxide Ring Opening Reactions.” Nature Commu. 2022, in press. Ren, D.; Lee, Y.-H.; Wang, S.-A.; Liu, H.-w. “Characterization of the Oxazinomycin Biosynthetic Pathway Revealing the Key Role of a Non-heme Iron-dependent Monooxygenase.” J. Am. Chem. Soc. 2022, 144, in press. Zhang, J.; Hou, X.; Chen, Z.; Ko, Y.; Ruszczycky, M. W.; Chen, Y.; Zhou, J,; Liu, H.-w. “Dioxane Bridge Formation in the Biosynthesis of Spectinomycin Involves a Twitch Radical SAM Dehydrogenase that Appears to Have Evolved from an Epimerase.” J. Am. Chem. Soc. 2022, 144, in press. Lin, W.-L.; Chen, J.-K.; Wen, X.; He, W.; Zarceno, G. A.; Chen, Y.; Chen, S.; Paull, T.; Liu, H.-w. ” DDX18 Prevents R-loop Induced DNA Damage and Genome Instability via PARP-1.” Cell Reports, 2022, in press. Lee, Y.-H.; Hou, X.; Chen, R.; Feng, J.; Liu, X.; Ruszczycky, M. W.; Guo, J.-M.; Wang, B.; Zhou, J.; Liu, H.-w. “Radical S-Adenosyl Methionine Enzyme BlsE Catalyzes a Radical Mediated 1,2-Diol Dehydration during the Biosynthesis of Blasticidin S.” J. Am. Chem. Soc. 2022, 144, 4478-4486.[PMC8934444] Lee, Y.-H.; Liu, H.-w. “Studies of GenK and OxsB, Two B12-Dependent Radical SAM Enzymes Involved in Natural Product Biosynthesis.” Meth. Enzymol. 2022, 677, 71-90. [NIHMSID1788471] Chen, T.-Y.; Zheng, Z.; Zhang, X.; Chen, J.; Cha, L.; Tang, Y.; Guo, Y.; Zhou, J.; Wang, B.; Liu, H.-w.; Chang, W.-c. “Decipher Reaction Pathway of Mononuclear Iron Enzymes Catalyzed N-C Triple Bond Formation in Isocyanide Lipopeptides and Polyketides Biosynthesis.” ACS Catalysis 2022, 12, 2270-2279. [NIHMS1778719] Joen, B.-s.; Huang, T.-Y.; Ruszczycky, M. W.; Choi, S.-h.; Kim, N.; Franklin, J. L.; Hung, S.-C.; Liu, H.-w. “Byproduct Formation During the Biosynthesis of Spinosyn A and Evidence for an Enzymatic Interplay to Prevent its Formation.” Tetrahedron 2021, in press. [NIHMSID1759956] Choi, S.-h.; Jeon, B.; Kim, N.; Wu, H.-H.; Ko, T.-P.; Ruszczycky, M. W.; Isiorho, E. A.; Liu, Y.-n.; Keatinge-Clay, A. T.; Tsai, M.-D.; Liu, H.-w. “Evidence for an Enzyme Catalyzed Rauhut-Currier Reaction during the Biosynthesis of Spinosyn A.” J. Am. Chem. Soc. 2021, 143, 20291-20295. [PMC8665079] Besandre, R.; Chen, Z.; David, I.; Zhang, J.; Ruszczycky, M. W.; Liu, A.; Liu, H.-w. “HygY is a Twitch Radical SAM Epimerase with Latent Dehydrogenase Activity Revealed upon Mutation of a Single Cysteine Residue.” J. Am. Chem. Soc. 2021, 143, 15152-15158. [PMC8611816] Ruszczycky, M. W.; Liu, H.-w. “Distinguishing Concerted versus Stepwise Mechanisms Using Isotope Effects on Isotope Effects.” Biochemistry 2021, 60, 3416-3418. [PMC8612942] Ren, D.; Kim, M.; Wang, S.-A.; Liu, H.-w. “Identification of a Pyrrole Intermediate Which Undergoes C-Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis.” Angew. Chem. Int. Ed. 2021, 60, 17148-17154. [PMC8292215] Yeh, Y.-C.; Kim, H. J.; Liu, H.-w. “Mechanistic Investigation of 1,2-Diol Dehydration of Paromamine Catalyzed by the Radical S-Adenosyl-L-methionine Enzyme AprD4.” J. Am. Chem. Soc. 2021, 143, 5038-5043. [PMC8045149] Zhong, A.; Lee, Y.-H.; Liu, Y.-n.; Liu, H.-w. “Biosynthesis of Oxetanocin A Includes a B12-dependent Radical SAM Enzyme Able to Catalyze both Oxidative Ring Contraction and the Demethylation of SAM.” Biochemistry 2021, 60, 537-546. [PMC7904626] Wang, S.-A.; Lin, C.-I.; Zhang, J.; Ushimaru, R.; Sasaki, E.; Liu, H.-w. “Studies of Lincosamide Formation Complete the Biosynthetic Pathway for Lincomycin A.” Proc. Natl. Acad. Sci. USA 2020, 117, 24794-24801. Zhang, J.; Fan, P.-H.; Lin, G.-M.; Chang, W.-C.; Liu, H.-w. “Recent Progress in the Biosynthesis of Carbohydrate-Containing Natural Products.” In Comprehensive Chemistry of Natural Product Chemistry, Liu, H-w.; Begley, T., Eds.; Elsvier: New York;. 2020, 336-392. Ren, D.; Ruszczycky, M. W.; Ko, Y.; Wang, S.-A.; Ogasawara, Y.; Kim, M.; Liu, H.-w. “Characterization of the Coformycin Biosynthetic Gene Cluster in Streptomyces kaniharaensis.” Proc. Natl. Aca. Sci. USA. 2020, 117, 10265-10270. [PMC7229688] Ushimaru, R.; Chen, Z.; Zhao, H.; Fan, P.-h.; Liu, H.-w. “Identification of the Enzymes Mediating the Maturation of the Sery-tRNA Synthetase Inhibitor SB-217452 during the Biosynthesis of Albomycins.” Angew. Chem. Int. Ed. 2019, 59, 3558-3562. [PMC7138408] Ruszczycky, M. W.; Liu, H.-w. “Measurement of Net Rate Constants from Enzyme Progress Curves without Numerical Curve Fitting.” Biochemistry. 2019, 58, 4950-4956. [PMC6910778].

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