IBC - 王彥士

研究領域與專長

實驗室研究方向主要著重於利用非典型氨基酸體內轉譯技術，探索蛋白質轉譯後修飾及其下游網絡交互作用，透過蛋白質化學，酵素學及化學生物學的研究方法，增進蛋白質轉譯後修飾在疾病模式下的了解，也進一步發展新穎蛋白質藥物。

目前研究計劃集中在三個方面:

發展合成均質蛋白質後修飾方法。經由生物體內嵌入非典型氨基酸，合成位置特異性均質類泛素修飾蛋白、甲基化蛋白及磷蛋白等，也進一步探討其生化機制和蛋白間交互作用。
生物催化。開發新型酵素可在生物體內對含嵌入非典型氨基酸蛋白質進行生物正交的新穎化學標記反應。
生物體內非典型氨基酸嵌入效率優化。進一步對原核及真核轉譯系統進行生物工程，以達到於生物體內嵌入多樣及多個非典型氨基酸於單一蛋白質中。

學經歷

2007 – 2012 博士, 化學系, Texas A&M University, USA
1999 – 2001 碩士, 化學系, 國立成功大學
1995 – 1999 學士, 化學系, 國立成功大學

2015 – 迄今助研究員, 中央研究院生物化學研究所
2012 – 2015 博士後研究, Department of Molecular Biophysics and Biochemistry, Medical School, Yale University, USA
2003 – 2007 研究助理, 中央研究院化學研究所

主要著作

Ferritin Conjugates With Multiple Clickable Amino Acids Encoded by C-Terminal Engineered Pyrrolysyl-tRNA Synthetase.
Wang YH, Jian ML, Chen PJ, Tsou JC, Truong LP, Wang YS*
Frontiers in chemistry (2021)

Revealing USP7 Deubiquitinase Substrate Specificity by Unbiased Syn-thesis of Ubiquitin Tagged SUMO2.
Jiang HK, Kurkute P, Li CL, Wang YH, Chen PJ, Lin SY, Wang YS*
Biochemistry (2020)

Probing the Active Site of Deubiquitinase USP30 with Noncanonical Tryptophan Analogues.
Jiang HK, Wang YH, Weng JH, Kurkute P, Li CL, Lee MN, Chen PJ, Tseng HW, Tsai MD, Wang YS*
Biochemistry (2020)

Linker and N-terminal domain engineering of pyrrolysyl-tRNA synthetase for substrate range shifting and activity enhancement.
Jiang HK, Lee MN, Tsou JC, Chang KW, Tseng HW, Chen KP, Li YK, Wang YS*
Front. Bioeng. Biotechnol. (2020)

Crystal structures reveal an elusive functional domain of pyrrolysyl-tRNA synthetase.
Suzuki T, Miller C, Guo LT, Ho JML, Bryson DI, Wang YS, Liu DR, Söll D
Nat. Chem. Bioli. (2017)

Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids.
Amiram M, Haimovich AD, Fan C, Wang YS, Aerni HR, Ntai I, Moonan DW, Ma NJ, Rovner AJ, Hong SH, Kelleher NL, Goodman AL, Jewett MC, Söll D, Rinehart J, Isaacs FJ
Nat. Biotechnol. (2015)

Probing the active site tryptophan of Staphylococcus aureus thioredoxin with an analog.
Englert M, Nakamura A, Wang YS, Eiler D, Söll D, Guo LT
Nucl. Acids Res. (2015)

Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.
Guo LT, Wang YS, Nakamura A, Eiler D, Kavran JM, Wong M, Kiessling LL, Steitz TA, O'Donoghue P, Söll D
Proc. Nalt. Acad. Sci. USA (2014)

Upgrading protein synthesis for synthetic biology.
O'Donoghue P, Ling J, Wang YS, Söll D
Nat. Chem. Biol. (2013)

A rationally designed pyrrolysyl-tRNA synthetase mutant with a broad substrate spectrum.
Wang YS, Fang X, Wallace AL, Wu B, Liu WR
J. Am. Chem. Soc. (2012)

著作列表

Jiang HK, Ambrose NL, Chung CZ, (Wang YS), Söll D*, Tharp JM* (2023-02) Proceedings of the National Academy of Sciences of the United States of America 120(8), e2219758120 "Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression."
Guo LT, Amikura K, Jiang HK, Mukai T, Fu X, (Wang YS), O'Donoghue P, Söll D, Tharp JM* (2022-11) Journal of Biological Chemistry 298(11), 102521 "Ancestral Archaea Expanded the Genetic Code with Pyrrolysine"
Wang D, Kao MR, Li J, Sun P, Meng Q, Vyas A, Liang PH, (Wang YS), Hsieh YSY* (2022-08) Journal of agricultural and food chemistry 70(32), 9941-9947 "Novel Two-Step Process in Cellulose Depolymerization: Hematite-Mediated Photocatalysis by Lytic Polysaccharide Monooxygenase and Fenton Reaction."
Wang YH, Jian ML, Chen PJ, Tsou JC, Truong LP, (Wang YS)* (2021-11) Frontiers in Chemistry 9, 779976 "Ferritin Conjugates With Multiple Clickable Amino Acids Encoded by C-Terminal Engineered Pyrrolysyl-tRNA Synthetase."
(Wang YS)*, Wu KP*, Jiang HK, Kurkute P, Chen RH* (2020-11) Molecules 25(21), 5200 "Branched Ubiquitination: Detection Methods, Biological Functions and Chemical Synthesis"
Jiang HK, Kurkute P, Li CL, Wang YH, Chen PJ, Lin SY, (Wang YS)* (2020-10) Biochemistry 59(40), 3796-3801 "Revealing USP7 Deubiquitinase Substrate Specificity by Unbiased Synthesis of Ubiquitin Tagged SUMO2."
Tseng HW, Baumann T, Sun H, (Wang YS), Ignatova Z, Budisa N (2020-09) Molecules 25(19), 4418 "Expanding the Scope of Orthogonal Translation with Pyrrolysyl-tRNA Synthetases Dedicated to Aromatic Amino Acids."
Jiang HK, Wang YH, Weng JH, Kurkute P, Li CL, Lee MN, Chen PJ, Tseng HW, Tsai MD, (Wang YS)* (2020-06) Biochemistry 59(24), 2205-2209 "Probing the Active Site of Deubiquitinase USP30 with Noncanonical Tryptophan Analogues."
Jiang HK, Lee MN, Tsou JC, Chang KW, Tseng HW, Chen KP, Li YK, (Wang YS)* (2020-04) Frontiers in bioengineering and biotechnology 8, 235 "Linker and N-terminal domain engineering of pyrrolysyl-tRNA synthetase for substrate range shifting and activity enhancement"
Tateki S, Corwin M, Guo LT, Ho JML, Bryson DI, (Wang YS), Liu DR, Söll D* (2017-12) Nature Chemical Biology 13(12), 1261-1266 "Crystal structures reveal an elusive functional domain of pyrrolysyl-tRNA synthetase"
Englert M, Vargas-Rodriguez O, Reynolds NM, (Wang Y S), Söll D*, Umehara T* (2017-11) BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1861(11 Pt B), 3009-3015 "A genomically modified Escherichia coli strain carrying an orthogonal E. coli histidyl-tRNA synthetase•tRNAHis pair."
Sharma V, (Wang YS), Liu WR* (2016-11) ACS Chemical Biology 11(12), 3305-3309 "Probing the catalytic charge-relay system in alanine racemase with genetically encoded histidine mimetic"
Amiram M, Haimovich AD, Fan CQ, (Wang YS), Aerni HR, Ntai I, Moonan DW, Ma NJ, Rovner AJ, Hong SH, Kelleher NL, Goodman AL, Jewett MC, Söll D*, Rinehart J*, and Isaacs FJ* (2015-12) Nature Biotechnology 33(12), 1272-1279 "Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids"
Englert M^†, Nakamura A^†, (Wang YS)^†, Eiler D, Söll D*, and Guo LT* (2015-12) Nucleic Acids Research 43 (22), 11061-11067 "Probing the active site tryptophan of Staphylococcus aureus thioredoxin with an analog"
Fan, C. Q.^†, Ho, J. M. H.^†, Chirathivat, N., Söll, D.* and (Wang, Y. S.)* (2014) ChemBioChem 15(12), 1805-1809 "Exploring the substrate range of wild-type aminoacyl-tRNA synthetases."
Tharp, J. M., (Wang, Y. S.), Lee, Y. J., Yang, Y., and Liu, W. R.* (2014) ACS Chemical Biology 9(4), 884-890 "Genetic incorporation of seven ortho-substituted phenylalanine derivatives."
Guo, L. T.^†, (Wang, Y. S.) ^†, Nakamura, A. ^†, Eiler, D. ^†, Kavran, J. M., Wong, M., Kiessling, L. L., Steitz, T. A., O’Donoghue, P.* and Söll, D.* (2014) Proceedings of the National Academy of Sciences of the United States of America 111(47), 16724-16729 "Polyspecific pyrrolysyl-tRNA synthetases from directed evolution."
Tuley, A., (Wang, Y. S.), Fang, X., Kurra, Y., Rezenom, Y. H., and Liu, W. R.* (2014) Chemical Communications 50(20), 2673-2675 "The genetic incorporation of thirteen novel non-canonical amino acids."
(Wang, Y. S.), Fang, X., Chen, H. Y., Wu, B., Wang, Z. U., Hilty, C., and Liu, W. R.* (2013) ACS Chemical Biology 8(2), 405-415 "Genetic incorporation of twelve meta-substituted phenylalanine derivatives using a single pyrrolysyl-tRNA synthetase mutant."
Ko, J. H. ^†, (Wang, Y. S.) ^†, Nakamura, A. ^†, Guo, L. T., Söll, D.*, and Umehara, T.* (2013) FEBS Letters 587(19), 3243-3248 "Pyrrolysyl-tRNA synthetase variants reveal ancestral aminoacylation function."
O'Donoghue, P. ^†, Ling, J. ^†, (Wang, Y. S.)^† and Söll, D.* (2013) Nature Chemical Biology 9(10), 594-598 "Upgrading protein synthesis for synthetic biology."
Wang, Z. ^†, (Wang, Y. S.) ^†, Pai, P. J., Russell, W. K., Russell, D. H. and Liu, R. W.* (2012) Biochemistry 51(26), 5232-5234 "A facile method to synthesize histones with posttranslational modification mimics."
(Wang, Y. S.), Fang, X., Wallace, A. L., Wu, B., and Liu, W. R.* (2012) Journal of the American Chemical Society 134(6), 2950-2953 "A rationally designed pyrrolysyl-tRNA synthetase mutant with a broad substrate spectrum."
Wan, W., (Wang, Y. S.), and Liu, R. W.* (2012) Organic Chemistry: Current Research 1(3), e111 "Genetically Encoding Bioorthogonal Functional Groups for Site-selective Protein Labeling."
Liu, W. R.*, (Wang, Y. S.), and Wan, W. (2011) Molecular Biosystems 7(1), 38-47 "Synthesis of proteins with defined posttranslational modifications using the genetic noncanonical amino acid incorporation approach."
(Wang, Y. S.), Russell, W. K., Wang, Z., Wan. W,, Dodd, L. E., Pai, P. J., Russell, D. H., and Liu, W. R.* (2011) Molecular Biosystems 7(3), 714-717 "The de novo engineering of pyrrolysyl-tRNA synthetase for genetic incorporation of L-phenylalanine and its derivatives."
(Wang, Y. S.), Wu, B., Wang, Z., Huang, Y., Wan, W., Russell, W. K., Pai, P. J., Moe, Y. N., Russell, D. H., and Liu, W. R.* (2010) Molecular Biosystems 6(9), 1557-1560 "A genetically encoded photocaged Nepsilon-methyl-L-lysine."
Ng, K. Y., Tu, L. C., (Wang, Y. S.), Chan, S. I., Yu, S. S.* (2008) ChemBioChem 9(7), 1116-1123 "Probing the hydrophobic pocket of the active site in the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath) by variable stereoselective alkane hydroxylation and olefin epoxidation."
Whang, T. J., Wang, Y. T., Wu, Y. P., (Wang, Y. S.), Tsai, M. C., and Huang, D. S.* (2005) SAR and QSAR in Environmental Research 16(3), 247-262 "Assessment of baseline toxicity of mono-cyclic aromatic compounds by pseudomonas initial oxygen uptake assay."
Huang, D. S.*, Whang, T. J., Cheng, F. C., Wu, Y. P., Wang, Y. T., Luo, W. I., and (Wang, Y. S.) (2005) Environmental Toxicology and Chemistry 24(2), 253-260 "Toxicity assessment of mono-substituted benzenes and phenols using a Pseudomonas initial oxygen uptake assay."
Yu, S. S., Chen, K. H., Tseng, M. Y., (Wang, Y. S.), Tseng, C. F., Chen, Y. J., Huang, D. S., and Chan, S. I.* (2003) Journal of Bacteriology 185(20), 5915-5924 "Production of high-quality particulate methane monooxygenase in high yields from Methylococcus capsulatus (bath) with a hollow-fiber membrane bioreactor."
Huang, D. S., Wu, S. H., (Wang, Y. S.), Yu, S. S., and Chan, S. I.* (2002) ChemBioChem 3(8), 760-765 "Determination of the carbon kinetic isotope effects on propane hydroxylation mediated by the methane monooxygenases from Methylococcus capsulatus (Bath) by using stable carbon isotopic analysis."
Wu, S. H., (Wang, Y. S.), Fan, L. X., Chang, R. T. D. and Huang, D. S.* (2002) Journal of the Chinese Chemical Society 79(3), 315-317 "Hydrous Pyrolysis of Methylphenanthrenes – Degradation and Isomerization."