Associate Professor Yew Wen Shan

Appointment(s)

Head, Department of Biochemistry, Yong Loo Lin School of Medicine

Assistant Dean (Graduate Studies), Yong Loo Lin School of Medicine

Deputy Director and Research Director, Synthetic Biology Translational Research Programme (SynBio TRP)

Deputy Director and Principal Investigator, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI)

Director, HH@NUS SINERGY Laboratory

Degree(s)

Biography

Associate Professor Yew Wen Shan is the Head of Department of Biochemistry at the National University of Singapore Yong Loo Lin School of Medicine. His other academic appointments include Assistant Dean (Graduate Studies), Deputy Director of the NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Deputy Director and Research Director of the Synthetic Biology Translational Research Programme, and Director of the HH@NUS SINERGY Laboratory. He is the current President of the Singapore Society for Biochemistry and Molecular Biology, and a Council Member of the Singapore National Academy of Science. He trained as a mechanistic enzymologist with Professor John A. Gerlt from the University of Illinois at Urbana-Champaign, laying the foundation for his career as a biochemistry professor and synthetic biology researcher.

His current and future research is centred on expanding the multi-faceted interface between enzymology, biological chemistry and synthetic biology, in an area he terms “synthetic enzymology”. In particular, his research is focused on the use of structural and mechanistic enzymological knowledge for protein engineering (exploring, defining and modulating substrate specificities), biocatalysis, biotransformation, therapeutic development (against metabolic diseases, infectious diseases, cancer and ageing), bioremediation (towards urban sustainability) and impactful maintenance of planetary health. 

His research is closely aligned with industrial needs and solutions, and he is currently part of the Wilmar@NUS Corporate Laboratory, the HH@NUS SINERGY Laboratory, the Centre for Precision Fermentation and Sustainability (PreFerS), the Bezos Centre for Sustainable Protein, and the National Centre for Engineering Biology of Singapore.

Research Areas/Research Interest

Research Excellence
My current and future research is centered on expanding the multi-faceted interface between enzymology and biological chemistry.
I have been successful in the use of structural and mechanistic enzymology for protein engineering, biocatalysis, therapeutic development and bioremediation. I have made significant contributions to the fields of quorum-based therapeutic development, enzyme design and engineering, synthetic biology, and bioremediation. I have led and defined Synthetic Enzymology as an exciting and promising field of translational research in synthetic biology.

Evidence of excellence in my research is represented by substantial research grant income ($3,764,863 in total grants as PI, $14,074,223 in total grants as Co-PI) and high-quality publications in top research journals (Biochemistry, Journal of Biological Chemistry, Antimicrobial Agents and Chemotherapy, Proceedings of the National Academy of Sciences USA, Journal of Molecular Biology, etc.). I have gained international recognition as an enzymologist and biochemist, as evidenced by invitations to:

Presentations in conferences, symposiums, and departmental talks in the US and Asia.
Service as expert reviewer in top research journals such as Nature, Biochemistry, Biochemical and Biophysical Research Communications, etc.
Chairing International Workshops and Symposiums.
Grant reviews for the French National Research Agency, the Singapore Agency for Science, Technology and Research, and the Singapore Ministry of Education.
Multi-institutional/national collaborative projects, including collaborations with industry such as Merck Research Laboratories, BD Biosciences and Cimelia Resource Recovery.

I will provide strong, visionary leadership in research by steering various synthetic biology-themed research programs at the Department (Co-program leader of SynBi@chemistry), Faculty (Coordinating PI of SBRP@NUHS), and University (Coordinating PI of SBRP@NUS and LSI2SB).
This leadership stems from my definition and expertise in Synthetic Enzymology for the purposeful production of compounds of biomedical and commercial importance, and purposeful bioremediation for environmental sustainability.

AY2015/2016
For the academic year AY15/16, I have published 3 research papers in the journals ACS Catalysis (IF=9.312), JoVE (IF=1.325) and Minerals Engineering (IF=1.714), and 1 review paper in the journal Molecules (IF=2.465). I have obtained a $512,200 MOE Tier 2 grant as PI, and together with my collaborators, I have obtained $1,423,000 million in grants as Co-PI. I am in the process of preparing other manuscripts for submission to ACS Synthetic Biology, Nature Communications and Biochemistry.

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:
Defining Synthetic Enzymology as an enabling platform for the Construction of Next-Generation Synthetic Biology solutions for Pharma and Consumer Businesses.
Using Synthetic Enzymology to discover and develop novel therapeutic biomolecules, in the areas of infectious diseases, metabolic disorders, cancer and aging.
Developing anti-virulence Quorum-Based Technology for use in the biomedical industry.
Using Synthetic Lixiviant Enzymology for Biomining of Electronic Wastes for Environmental Sustainability.
Development of Lead Compounds Targeting Enzymes involved in Metabolic Cancer.
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:

Rational design and directed evolution of enzymatic activities.
Drug design and therapeutics against infectious diseases, metabolic disorders, cancer and aging.
Synthetic Enzymology for biomedical and bioremediation applications.
Deciphering enzyme specificity.
Mechanistic enzymology of enzymes of pharmaceutical and industrial importance.
Discovery of new enzymatic functions.

Selected Publications

Engineering a Metal Reductase for the Bioremediation of Anthropogenic Electronic Wastes: From Hg(II) to Au(III) and Ag(I) Enzymatic Reduction

Jasmine Puay Suan Chua, Rashmi Rajasabhai, Wei Zhe Teo, Bo Xue, and Wen Shan Yew*

A biological camera that captures and stores images directly into DNA

Cheng Kai Lim, Jing Wui Yeoh, Aurelius Andrew Kunartama, Wen Shan Yew & Chueh Loo Poh

Engineered Nucleotide Chemicapacitive Microsensor Array Augmented with Physics-Guided Machine Learning for High-Throughput Screening of Cannabidiol.2022 May 6. Doi: 10.1002/smll.202107659

Stephanie Hui Kit Yap, Jieming Pan, Dao Viet Linh, Xiangyu Zhang, Xinghua Wang, Wei Zhe Teo, Evgeny Zamburg, Chen-Khong Tham, Wen Shan Yew, Chueh Loo Poh, Aaron Voon-Yew Thean

Structure-Guided Engineering of Prenyltransferase NphB for High-Yield and Regioselective Cannabinoid Production

Kevin Jie Han Lim, Yossa Dwi Hartono, Bo Xue, Maybelle Kho Go, Hao Fan*, and Wen Shan Yew*

Reconstituting the complete biosynthesis of D-lysergic acid in yeast

Garrett Wong, Li Rong Lim, Yong Quan Tan, Maybelle Kho Go, David J. Bell, Paul S. Freemont & Wen Shan Yew

Scalable Workflow for Green Manufacturing: Discovery of Bacterial Lipases for Biodiesel Production

Jeng Yeong Chow, Kimberly Li Shi Choo, Yan Ping Lim, Lay Hiang Ling, Giang Kien Truc Nguyen, Bo Xue, Nam Hai Chua, and Wen Shan Yew*

Structure of a Minimal α-Carboxysome-Derived Shell and Its Utility in Enzyme Stabilization

Yong Quan Tan, Samson Ali, Bo Xue, Wei Zhe Teo, Lay Hiang Ling, Maybelle Kho Go, Hong Lv, Robert C. Robinson, Akihiro Narita, and Wen Shan Yew*

Novel Modalities in DNA Data Storage

Cheng Kai Lim, Saurabh Nirantar, Wen Shan Yew, Chueh Loo Poh

Evolving a Thermostable Terminal Deoxynucleotidyl Transferase

Jasmine Puay Suan Chua, Maybelle Kho Go, Trina Osothprarop, Seth Mcdonald, Alexander G. Karabadzhak, Wen Shan Yew*, Sergio Peisajovich*, and Saurabh Nirantar*

Directed Computational Evolution of Quorum-Quenching Lactonases from the Amidohydrolase Superfamily

Maybelle Kho Go, Li Na Zhao, Bo Xue, Shreyas Supekar, Robert C. Robinson, Hao Fan, Wen Shan Yew

Toolkit Development for Cyanogenic and Gold Biorecovery Chassis Chromobacterium violaceum

Lu Ting Liow, Maybelle Kho Go, Matthew Wook Chang, and Wen Shan Yew*

Building a global alliance of biofoundries

Hillson, N., et. al. Yew, W.S., Yuan, Y., Zhao, H., and Freemont, P.S.

Synthetic Enzymology and the Fountain of Youth: Repurposing Biology for Longevity

Yan Ping Lim, Maybelle K. Go, Manfred Raida, Takao Inoue, Markus R. Wenk, Jay D. Keasling, Matthew W. Chang, and Wen Shan Yew*

Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention

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.

Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes

Pham, H.L., Wong, A., Chua, N., Teo, W.S., Yew, W.S., Chang, M.W.

Synthetic Polyketide Enzymology: Platform for Biosynthesis of Antimicrobial Polyketides

Go, M.K., Wongsantichon, J., Cheung, V.W.N., Chow, J.Y., Robinson, R.C., and Yew, W.S.

Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family

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.

Glycine Decarboxylase Is an Unusual Amino Acid Decarboxylase Involved in Tumorigenesis

Go, M.K., Zhang, W.C., Lim, B., and Yew, W.S.

Structural Evidence of a Productive Active Site Architecture for an Evolved Quorum-quenching GKL Lactonase

Xue, B., Chow, J.Y., Baldansuren, A., Yap, L.L., Gan, Y.W., Dikanov, S.A., Robinson, R.C., and Yew, W.S.

Establishing a Toolkit for Precursor-Directed Polyketide Biosynthesis: Exploring Substrate Promiscuities of Acid-CoA Ligases

Go, M.K., Chow, J.Y., Cheung, V.W.N., Lim, Y.P., and Yew, W.S.