YEW Wen Shan

Associate Professor

Affiliations

Associate Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS.
Deputy Director and 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.
Deputy Chairman (Programme Outreach), NUS Medicine Graduate Programme Committee.
President, Singapore Society for Biochemistry and Molecular Biology.

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. Lim, Y.P., Go, M.K., Raida, M., Inoue, T., Wenk, M.R., Keasling, J.D., Chang, M.W., and Yew, W.S. (2018) Synthetic Enzymology and the Fountain of Youth: Repurposing Biology for Longevity. ACS Omega.

  2. Lubkowicz, D., Ho, C.L., Hwang, I.Y., Yew, W.S., Lee, Y.S., and Chang, M.W. (2018) Reprogramming Probiotic Lactobacillus reuteri as a Biosensor for Staphylococcus aureus Derived AIP-I Detection. ACS Synth Biol. 7(5):1229-1237.

  3. Go, M.K., Chow, J.Y., and Yew, W.S. (2018) Directed Evolution of Quorum-Quenching Enzymes: A Method for the Construction of a Directed Evolution Platform and Characterization of a Quorum-Quenching Lactonase from Geobacillus kaustophilus. Methods Mol Biol. 1673:311-323.

  4. Ho, C.L., Tan, H.Q., Chua, K.J., Kang, A., Lim, K.H., Ling, K.L., Yew, W.S., Lee, Y.S., Thiery, J.P., and Chang, M.W. (2018) Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nature Biomedical Engineering. 2:27-37.

  5. Pham, H.L., Wong, A., Chua, N., Teo, W.S., Yew, W.S., Chang, M.W. (2017) Engineering a Riboswitch-based Genetic Platform for the Self-directed Evolution of Acid-tolerant Phenotypes. Nature Commun. 8(1):411

  6. Lim, Y.P., Go, M.K., and Yew, W.S. (2016) Exploiting the Biosynthetic Potential of Type III Polyketide Synthases. Molecules Jun 22: 21(6). pii: E806. doi: 10.3390/molecules21060806.

  7. Go, M.K., Wongsantichon, J., Cheung, V.W.N., Chow, J.Y., Robinson, R.C., and Yew, W.S. (2015) Synthetic Polyketide Enzymology: Platform for Biosynthesis of Novel Anti-Microbial Polyketides. ACS Catalysis 5(7): 4033–4042.

  8. 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.

  9. 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.

  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.