Wen Shan YEW

Associate Professor

Affiliations

Associate Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS.
Principal Investigator, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI).
Technical Member, Singapore Consortium for Synthetic Biology (SINERGY).
Supervisor, NUS Graduate School for Integrative Sciences and Engineering (NGS).
Deputy Chair, Masters in Environmental Management (MEM) PMC.

Education

Degree and Institution Year(s)
Ph.D. Biochemistry, University of Illinois at Urbana-Champaign, USA 2004
M.S., Biochemistry, University of Illinois at Urbana-Champaign, USA 2002
B.Sc., Biochemistry, National University of Singapore 1999

Professional Experience

Position and Institute Year(s)
Associate Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS 2015–present
Assistant Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS 2007–2015
Assistant Professor of Biological and Medical Science, Division of Engineering, Science and Technology, University of New South Wales Asia, Singapore 2007
Postdoctoral Research Associate, Department of Biochemistry, University of Illinois at Urbana-Champaign, USA 2004-2006
Herbert E. Carter Fellow, University of Illinois at Urbana-Champaign, USA 2002-2003
A*STAR International Fellow, University of Illinois at Urbana-Champaign, USA 2002-2003

Research Interest

As a continuation and elaboration of my interests in enzymology, my current and future research is centered on expanding the multi-faceted interface between enzymology and biological chemistry. In particular, my research is focused on the use of structural and mechanistic enzymological knowledge for protein engineering (exploring, defining and modulating substrate specificities), biocatalysis, therapeutic development (against infectious diseases, cancer and ageing) and bioremediation (towards urban sustainability). Significant contributions to the field of quorum-based therapeutic development were made through efforts in delineating the underlying principles of enzyme design and engineering. The first demonstration of the use of recombinant quorum-quenching enzymes in the disruption of biofilm formation (vis a vis reduction in bio-mass and thickness) by a major human pathogen, Acinetobacter baumannii, associated with multi-drug resistant nosocomial infections, was made. We have begun defining Synthetic Enzymology as the application of enzymological principles in Synthetic Biology (in which enzymes are often employed in the biosynthesis of compounds for purposeful function) and describe its use as an enabling platform in Synthetic Biology for the purposeful production of compounds of biomedical and commercial importance. We have also begun defining Synthetic Enzymology as a means for purposeful bioremediation, and demonstrated the feasibility and utility of synthetic cyanogenesis (cyanogenesis refers to the biosynthesis of cyanide, and synthetic cyanogenesis refers to cyanogenesis through synthetic enzymological means). This is part of the overall aim to establish synthetic lixiviant biology as a means to recover precious metals (such as gold) and remove toxic metals (such as lead and mercury) from electronic waste. Lixiviants are (bio)chemicals that can extract (or leach) metals from a source (such as ores and minerals, or electronic waste in our context).

Current research interest focuses on protein engineering and biocatalysis, with emphasis on using structural and mechanistic enzymological knowledge to develop therapeutics. We are involved in the following research areas:
1. Defining Synthetic Enzymology as an enabling platform for the Construction of Next-Generation Synthetic Biology solutions for Pharma and Consumer Businesses.
2. Using Synthetic Enzymology to discover and develop novel therapeutic biomolecules, in the areas of infectious diseases, metabolic disorders, cancer and aging.
3. Developing anti-virulence Quorum-Based Technology for use in the biomedical industry.
4. Using Synthetic Lixiviant Enzymology for Biomining of Electronic Wastes for Environmental Sustainability.
5. Development of Lead Compounds Targeting Enzymes involved in Metabolic Cancer.
6. Using Synthetic Enzymology for the Construction of Therapeutic (Probiotic) Cells for the Treatment of Metabolic Diseases and Infectious Diseases.

Major research interests can be classified as follows:
1. Rational design and directed evolution of enzymatic activities.
2. Drug design and therapeutics against infectious diseases, metabolic disorders, cancer and aging.
3. Synthetic Enzymology for biomedical and bioremediation applications.
4. Deciphering enzyme specificity.
5. Mechanistic enzymology of enzymes of pharmaceutical and industrial importance.
6. Discovery of new enzymatic functions.

Selected Publications

  1. Go, M.K., Wongsantichon, J., Cheung, V.W.N., Chow, J.Y., Robinson, R.C., and Yew, W.S. (2015) Synthetic Polyketide Enzymology: A Platform for Biosynthesis of Novel Anti-Microbial Polyketides. ACS Catalysis (in press)

  2. Tay, S.B., Chow, J.Y., Go, M.K., and Yew, W.S. (2015) Anti-Virulent Disruption of Pathogenic Biofilms Using Engineered Quorum-Quenching Lactonases. JoVE (in press)

  3. Cheung, V.W.N., Xue, B., Hernandez-Valladares, M., Go, M.K., Tung, A., Aguda, A.H., Robinson, R.C., and Yew, W.S.(2014) Identification of Polyketide Inhibitors Targeting 3-Dehydroquinate Dehydratase in the Shikimate Pathway of Enterococcus faecalis. PLoS One 9(7):e103598.

  4. Odokonyero, D., Sakai, A., Patskovsky, Y., Malashkevich, V.N., Fedorov, A.A., Bonanno, J.B., Fedorov, E.V., Toro, R., Agarwal, R., Wang, C., Ozerova, N.D.S., Yew, W.S., Sauder, J.M., Swaminathan, S., Burley, S.K., Almo, S.C., and Glasner, M.E. (2014) Loss of Quaternary Structure is Associated with Rapid Sequence Divergence in the OSBS Family. Proc Natl Acad Sci 111, 8535-8540.

  5. Go, M.K., Zhang, W.C., Lim, B., and Yew, W.S. (2014) Glycine Decarboxylase is an Unusual Amino Acid Decarboxylase Involved in Tumorigenesis. Biochemistry 53, 947-956.

  6. Chow, J.Y., Yang, Y., Tay, S.B., Chua, K.L., and Yew, W.S. (2014) Disruption of Biofilm Formation by the Human Pathogen Acinetobacter baumannii using Engineered Quorum-quenching Lactonases. Antimicrob Agents Chemother. 58, 1802-1805.

  7. Tay, S.B., and Yew, W.S. (2013) Development of Quorum-Based Anti-Virulence Therapeutics Targeting Gram-Negative Bacterial Pathogens. Int J Mol Sci. 14, 16570-16599. doi: 10.3390/ijms140816570.

  8. Tay, S.B., Natarajan, G., Rahim, M.N., Tan, H.T., Chung, M.C., Ting, Y.P., and Yew, W.S. (2013) Enhancing gold recovery from electronic waste via lixiviant metabolic engineering in Chromobacterium violaceum. Sci Rep. 3, 2236. doi: 10.1038/srep02236.

  9. Xue, B., Chow, J.Y., Baldansuren, A., Yap, L.L., Gan, Y.W., Dikanov, S.A., Robinson, R.C., and Yew, W.S. (2013) Structural Evidence of a Productive Active Site Architecture for an Evolved Quorum-quenching GKL Lactonase. Biochemistry 52, 2359-2370.

  10. Go, M.K., Chow, J.Y., Cheung, V.W.N., Lim, Y.P., and Yew, W.S. (2012) Establishing a Toolkit for Precursor-directed Polyketide Biosynthesis: Exploring Substrate Promiscuities of Acid-CoA Ligases. Biochemistry 51, 4568-4579.

  11. Chow, J.Y., Xue, B., Lee, K.H., Tung, A., Wu, L., Robinson, R.C., and Yew, W.S. (2010) Directed evolution of a thermostable quorum-quenching lactonase from the amidohydrolase superfamily. J Biol Chem. 285, 40911-40920.

  12. Huang, S., Chua, J.H., Yew, W.S., Sivaraman, J., Moore, P.K., Tan, C.H., and Deng, L.W. (2010) Site-directed mutagenesis on human cystathionine-gamma-lyase reveals insights into the modulation of H2S production. J Mol Biol. 396, 708-718.

  13. Chow, J.Y., Long, W., and Yew, W.S. (2009) Directed Evolution of a Quorum-Quenching Lactonase from Mycobacterium avium subsp. paratuberculosis K-10 in the Amidohydrolase Superfamily. Biochemistry 48, 4344-4353.

  14. Yew, W.S., Fedorov, A.A., Fedorov, E.V., Almo, S.C., and Gerlt, J.A. (2007) Evolution of Enzymatic Activities in the Enolase Superfamily: L-Talarate/Galactarate Dehydratase from Salmonella typhimurium LT2. Biochemistry 46, 9564-9577.

  15. Yew, W.S., Fedorov, A.A., Fedorov, E.V., Wood, B.M., Almo, S.C., and Gerlt, J.A. (2006) Evolution of Enzymatic Activities in the Enolase Superfamily: D Tartrate Dehydratase from Bradyrhizobium japonicum. Biochemistry 45, 14598-14608.

  16. Yew, W.S., Fedorov, A.A., Fedorov, E.V., Rakus, J.F., Pierce, R.W., Almo, S.C., and Gerlt, J.A. (2006) Evolution of Enzymatic Activities in the Enolase Superfamily: L-Fuconate Dehydratase from Xanthomonas campestris. Biochemistry 45, 14582-14597.

  17. Sakai, A., Xiang, D.F., Xu, C., Song, L., Yew, W.S., Raushel, F.M., and Gerlt, J.A. (2006) Evolution of Enzymatic Activities in the Enolase Superfamily: N-Succinylamino Acid Racemase and a New Pathway for the Irreversible Conversion of D- to L-Amino Acids. Biochemistry 45, 4455-4462.

  18. Wise, E.L., Yew, W.S., Akana, J., Gerlt, J.A., and Rayment, I. (2005) Evolution of Enzymatic Activities in the Orotidine 5'-Monophosphate Decarboxylase Suprafamily: Structural Basis for Catalytic Promiscuity in Wild-type and Designed Mutants of 3-Keto-L-Gulonate 6-Phosphate Decarboxylase. Biochemistry 44, 1816-1823.

  19. Yew, W.S., Akana, J., Wise, E.L., Rayment, I., and Gerlt, J.A. (2005) Evolution of Enzymatic Activities in the Orotidine 5'-Monophosphate Decarboxylase Suprafamily: Enhancing the Promiscuous D-Arabino-Hex-3-ulose 6-Phosphate Synthase Reaction Catalyzed by 3-Keto-L-Gulonate 6-Phosphate Decarboxylase. Biochemistry 44, 1807-1815.

  20. Wise, E.L., Yew, W.S., Rayment, I., and Gerlt, J.A. (2004) Evolution of Enzymatic Activities in the Orotidine 5’ Monophosphate Decarboxylase Suprafamily: Crystallographic Evidence for a Proton Relay System in the Active Site of 3-Keto-L-Gulonate 6 Phosphate Decarboxylase. Biochemistry 43, 6438-6446.

  21. Yew, W.S., Wise, E.L., Rayment, I., and Gerlt, J.A. (2004) Evolution of Enzymatic Activities in the Orotidine 5’ Monophosphate Decarboxylase Suprafamily: Mechanistic Evidence for a Proton Relay System in the Active Site of 3-Keto-L-Gulonate 6 Phosphate Decarboxylase. Biochemistry 43, 6427-6437.

  22. Wise, E.L., Yew, W.S., Gerlt, J.A., and Rayment, I. (2003) Structural Evidence for a 1,2-Enediolate Intermediate in the Reaction Catalyzed by 3-Keto-L-Gulonate 6-Phosphate Decarboxylase, a Member of the Orotidine 5'-Monophosphate Decarboxylase Suprafamily. Biochemistry 42, 12133-12142.

  23. *Wise, E.L., *Yew, W.S., Babbitt, P.C., Gerlt, J.A., and Rayment, I. (2002) Homologous (/)8-Barrel Enzymes that Catalyze Unrelated Reactions: Orotidine 5’-Monophosphate Decarboxylase and 3-Keto-L-Gulonate 6-Phosphate Decarboxylase. Biochemistry 41, 3861-3869. *equal authorship, Highlighted in Editor’s Choice, Science (2002) 295, 1975.

  24. Yew, W.S., and Gerlt, J.A. (2002) Utilization of L-Ascorbate by Escherichia coli K-12: Assignments of Function to Products of the yjf-sga and yia-sgb Operons. J Bacteriol 184, 302-306.

  25. Yew, W.S., and Khoo, H.E. (2000) The Role of Tryptophan Residues in the Hemolytic Activity of Stonustoxin, a Lethal Factor from Stonefish (Synanceja horrida) Venom. Biochimie 82, 251-257.