Wen Shan YEW

Head of Department
Department of Biochemistry
Yong Loo Lin School of Medicine
National University of Singapore

Associate Professor of Biochemistry (Tenured)
Department of Biochemistry
Synthetic Biology for Clinical and Technological Innovation
Yong Loo Lin School of Medicine
National University of Singapore

Postdoctoral Research Associate
Department of Biochemistry
University of Illinois at Urbana-Champaign

Graduate Research Assistant
Department of Biochemistry
University of Illinois at Urbana-Champaign

Graduate Teaching Assistant
Department of Chemistry
University of Illinois at Urbana-Champaign

Teaching Assistant
Department of Biochemistry
National University of Singapore

Undergraduate Research Assistant
Department of Biochemistry
National University of Singapore

Reviewer for eLife

Editorial Board member, Biotechnology Notes

Special Issue Editor for Cells

Editorial Board member, IET Engineering Biology; Associate Editor, 3Biotech

President, Singapore Society for Biochemistry and Molecular Biology;

Reviewer for US-Israel Binational Science Foundation (BSF);

Reviewer for Biotechnology and Biological Sciences Research Council (BBSRC), United Kingdom

Reviewer for ChemComm, Chemical Science, Biotechnology and Bioengineering, Chemical Engineering Science.

Open Life Sciences, Genetics and Molecular Biology, Oncology Research and Treatment, Biotechnology for Biofuels, RSC Advances

Reviewer for PLOS One

Reviewer for Biochemistry, Microbial Informatics and Experimentation, Biochemical Journal, Central European Journal of Biology, Molecules

Member, American Society for Microbiology

Associate Editorial Board member of International Journal of Biochemistry and Molecular Biology

Expertise Grant Reviewer for the French National Research Agency (Agence Nationale de la Recherche)

Reviewer for Nature, Trends in Biochemical Sciences

Reviewer for ChemBioChem, Biochemical and Biophysical Research Communications

Reviewer for FEBS Letters

Grant Reviewer for A*STAR, Ministry of Education

Member, American Society for Biochemistry and Molecular Biology

Member, American Chemical Society

Annual Teaching Excellence Award
National University of Singapore

Educator of the Year Award
Yong Loo Lin School of Medicine
National University of Singapore

Annual Teaching Excellence Award
National University of Singapore

Singapore National Academy of Science Award in Biochemistry

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). Our mechanistic studies of the human enzyme glycine decarboxylase, identified as a metabolic oncogene in multiple cancer types, have significantly advanced efforts in drug development against metabolic cancer; we are currently in collaboration with Merck Research Laboratories (MRL) to jointly develop potential lead compounds targeting serine-glycine metabolic enzymes (including glycine decarboxylase) implicated in cancer progression.

1. Defining Synthetic Isoprenoid Enzymology as an enabling platform for the Construction of Next-Generation Synthetic Biology solutions for nutrichemical production.
2. Using Synthetic Enzymology to discover and develop novel Polyketide-based therapeutic biomolecules, in the areas of infectious diseases, 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.

1. Rational design and directed evolution of enzymatic activities.
2. Drug design and therapeutics against infectious diseases, cancer and aging.
3. Synthetic Enzymology for biomedical and bioremediation applications.
4. Deciphering enzyme specificity.
5. Mechanistic enzymology of enzymes of pharmaceutical importance.
6. Discovery of new enzymatic functions.

• Singapore Patent Application No. 10202010547W filed on 23 Oct 2020: Bacterial Microcompartment Virus-like Particles.

• US Patent Application No. US 63/023,734 filed on 12 May 2020: Thermostable Terminal Deoxynucleotidyl Transferase.

• International Patent Application No. PCT/SG2020/050216 filed on 8 Apr 2020: Using Synthetic Lixiviant Biology for the Recovery of Precious and Toxic Metals from Anthropogenic Sources. (ILO Ref: 16032N-05)

• International Patent Application No. PCT/SG2020/050584 filed on 12 Oct 2020: Sustainable Production of Cannabinoids From Simple Precursor Feedstocks Using Saccharomyces Cerevisae. (ILO Ref: 2019-345-01)

• International Patent Application No. PCT/SG2020/050582 filed on 12 October 2020: Biosynthesis of Cannabinoid Precursors Using Novel Aromatic Prenyl Transferases. (ILO Ref: 2019-344-01)

• International Patent Application No. PCT/SG2020/050583 filed on 12 October 2020: Biosynthesis of Cannabinoids From Cannabigerolic Acid Using Novel Cannabinoid Synthases. (ILO Ref: 2019-338-01)

• Singapore Non-Provisional Application No. 10201904705X filed on 24 May 2019: Using Synthetic Lixiviant Biology for the Recovery of Precious and Toxic Metals from Anthropogenic Sources. (ILO Ref: 16032N-04)

• Singapore Patent Application No. 10201903117U filed on 8 April 2019: Using Enzymes To Break Down Cyanide and Synthetic Metal Recovery For Synthetic Lixiviant Biology. (ILO Ref: 16032N-03)

• Singapore Patent Application No. 10201400929P filed 25 March 2014: GLDC Inhibitors I – 6-Membered Heterocycle Compounds.

• Singapore Patent Application No. 10201400930T filed 25 March 2014: GLDC Inhibitors II – 5-Membered Heteroaryl Compounds.

• US Provisional No. 61844550 filed Jul 10 2013: Genetically-Engineered Chromobacterium Violaceum with Enhanced Cyanide Lixiviant Production for Bioleaching of Precious Metal from Electronic Waste.

• School of Biological Sciences, Nanyang Technological University Webinar (26 Oct 2020).

• EDB Industrial Biotechnology Webinar (29 Sep 2020).

• Conference on Nano-Micromaterials for Circular Economy and Sustainability (Aug 29 – 01 Sep 2019), NUS and NSF USA and Global Initiatives, Singapore.

• Engineering Biology Research Consortium (EBRC) Global Forum for Engineering Biology: Initial Review of Synthetic Biology National Strategies Workshop (Sep 9-10 2019), Santa Cruz, USA.

• Keynote Presentation at the Asian Synthetic Biology Association Symposium (Oct 26-29 2019) Chengdu, China.

• AOARD (Nov 4-5 2019), Dayton, USA.

• Department of Biochemistry, University of Illinois (5 June 2019), Illinois, USA.

• Global BioFoundries Alliance Conference (9-10 May 2019), Kobe University, Japan.

• 1^st Asian Synthetic Biology Association Conference 2018 (22-25 Nov 2018) at Hyatt Regency JEJU, Korea.

• Global BioFoundries Meeting (20-21 June 2018), Royal School of Mines, Imperial College, London.

• BioSystems Design 4.0 2018 (10-11 May 2018) at Biopolis, Singapore.

• ICBE Asia 2018 International Conference on Biomolecular Engineering (8-10 Jan 2018) at Singapore.

• IBN-MOE Symposium on Science: Frontiers in Biology Program 2017 (15 Nov 2017) at Biopolis, Singapore.

• Biosynthetic Forum (16 Oct 2017) at Wilmar Biotechnology Research & Development Center, Shanghai, China.

• Engineering Biology Research Consortium (EBRC) 2017 Strategic Fall Retreat (22 and 23 Sep 2017) at Georgia Tech, USA.

• International Union of Microbiological Societies (IUMS) 2017 (17 – 21 July 2017), Singapore.

• GP-write Meeting 2017 (9-10 May 2017) at the Center of Excellence for Engineering Biology, New York.

• “Towards Resource Recovery in a Circular Economy” Workshop (21 Apr 2017) organized by The Holland Innovation Network at the Embassy of the Kingdom of the Netherlands, Singapore.

• BioSystems Design 3.0 2017 (16-17 Feb 2017) at Biopolis, Singapore.

• IET/SynbiCITE Engineering Biology Conference 2016 (13 -15 Dec 2016) at IET London, Savoy Place, UK.

• 16^th International Conference on Biomedical Engineering (7-10 Dec 2016)

• Department of Medicine, Imperial College London (16 Feb 2016)

• AICHE Metabolic Engineering Conference (5 Jan 2016)

• NUS-BTI Synthetic Biology Workshop (13 Nov 2015)

• University of Edinburgh-NUS Synthetic Biology Workshop (26 Oct 2015)

• Imperial College-NUS Synthetic Biology Workshop (23 Oct 2015)

• NUS-Edinburgh Synthetic Biology Symposium 2015 (4 May 2015)

• Biosystems Design 1.0, NUS and A*STAR (9 – 10 Feb 2015)

• Biochemical Engineering Seminar Series, A*STAR (19 Jun 2014)

• UK-Singapore Synthetic Biology Workshop, NUS and A*STAR (18-19 Feb 2014)

• NUS-POSTECH Symposium in Biochemistry, National University of Singapore (5 Feb 2014)

• Department of Pharmaceutical Chemistry, University of California at San Francisco (12 Nov 2013)

• Department of Biochemistry, University of Illinois (8 Nov 2013)

• Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University (5 Nov 2013)

• Foster Colloquium Series, Department of Chemistry, University at Buffalo (1 Nov 2013)

• Department of Chemistry and Chemical Biology, University of New Mexico (13 Sep 2013)

• Department of Molecular Biology and Biochemistry, University of California at Irvine (12 Sep 2013)

• Division of Medicinal Chemistry, University of Texas at Austin (10 Sep 2013)

• Department of Chemistry, University of Utah (5 Sep 2013)

• Alternative Aviation Fuel in Asia Conference & ASEAN Algae Biofuel Initiative Conference (2012)

• College of Chemistry and Molecular Engineering, Peking University (2011)

• World Congress of Microbes-Symposium of Antiparasites, Beijing (2011)

• Biofuels Workshop, Department of Biological Sciences, NUS (2011)

• BIRC Workshop on Protein Structure and Function Prediction, Nanyang Technological University (2008)

• NRF Engineering Biology Workshop, Temasek Lifesciences Laboratory (2007)

• Trust of Urbana Award Talk, University of Illinois at Urbana-Champaign (2006)

• Post-doctoral Fellows:
  • Dr Wu Long (alumni)
  • Dr Yu Kai (alumni)
  • Dr Cheah Wai Yuen (alumni)
  • Dr Wan Ke Yan (alumni)
  • Dr Sim Wen Jing (alumni)
  • Dr Morphy Dumlao (alumni)
  • Dr Maybelle Darlene Kho Go (alumni)
  • Dr Chow Jeng Yeong (alumni)
  • Dr Lim Yan Ping
  • Dr Liow Lu Ting
  • Dr Teo Wei Zhe
  • Dr Xue Bo (alumni)
  • Dr Han Ping
  • Dr Yossa Dwi Hartono

• Post-graduate Students:
  • Chow Jeng Yeong, Ph.D., graduated July 2013. (NGS)
  • Aishwarya, S. MSc., graduated July 2013.
  • Cheung Wing Ngar Vivian, Ph.D., graduated Jan 2014.
  • Lim Yan Ping, Ph.D., graduated July 2016.
  • Tay Song Buck, Terence, Ph.D., graduated July 2017.
  • Rashmi Rajasabhai, Ph.D., graduated July 2018.
  • Liow Lu Ting, Ph.D., graduated July 2019.
  • Wong Wei Jie, Garrett, Ph.D. (Imperial College-NUS Joint Ph.D.), graduated July 2020.
  • Tan Yong Quan, Ph.D. (NGS), graduated July 2020.
  • Chua Puay Suan, Jasmine, Ph.D. (Illumina-NUS EDB-IPP), graduated July 2020.
  • Lim Li Rong, Ph.D. candidate. (NGS)
  • Lim Jie Han Kevin, Ph.D. candidate.
  • Loh Yuen Nee Yvonne, Ph.D. candidate.
  • Juztin James Tong Yi Sheng, Ph.D. candidate. (Wilmar-NUS EDB-IPP)
  • Andre Ng Mong Jie, Ph.D. candidate. (Wilmar-NUS EDB-IPP)
  • Lim Dingjie, Jonathan, Ph.D. candidate.
  • Lim Cheng Kai, Ph.D. candidate. (NGS)
  • Chua Yuen Siong, Ph.D. candidate.
  • Ling Lay Hiang, Ph.D. candidate. (NGS)
  • Miselle Tiana Hengardi, Ph.D. candidate (AGS)
  • Teo Zhi Ting, Ph.D. candidate (Agilent-NUS EDB-IPP)

1. Go, M.K., Zhao, L.N., Xue, B., Supekar, S., Robinson, R.C., Fan, H., and Yew, W.S. (2020) Directed Computational Evolution of Quorum-Quenching Lactonases from the Amidohydrolase Superfamily. Structure 28, 1-8. June 2. doi: 10.1016/j.str.2020.03.011.

 

2. Liow, L.T., Go, M.K., Chang, M.W., and Yew, W.S. (2020) Toolkit Development for Cyanogenic and Gold Biorecovery Chassis Chromobacterium violaceum. ACS Synth Biol. 9(4), 953-961. March 11. doi: 10.1021/acssynbio.0c00064.

 

3. 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 3(9): 11050-11061. doi: 10.1021/acsomega.8b01620.

 

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. www.nature.com/articles/s41551-017-0181-y.

 

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. www.nature.com/articles/s41467-017-00511-w.

 

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. doi: 10.1021/acscatal.5b00477.

 

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. doi: 10.1021/bi4014227.

 

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. doi: 10.1021/bi300425j.