Dr. Stephen Seah

Dr. Stephen Seah
Associate Professor
Department of Molecular and Cellular Biology
Phone number: 
56750 / 53026
SSC 4250
SSC 4205A

I have always been fascinated by how proteins, made up of simple building blocks of 20 amino acids, could serve the diverse functions required in living systems. I have previously worked with Reiske iron-sulphur proteins (M.Sc. research), phenylalanine dehydrogenase (Ph.D. research) and C-C bond cleaving hydrolases (Postdoctoral work in Université Laval and University of British Columbia). In Guelph, my lab is studying enzymes related by convergent and divergent evolution to decipher structure-function relationships in proteins.  Target enzymes being investigated include those important for environmental pollutant degradation and those that are medically relevant for development of new therapeutic drugs.

  • B.Sc. National University of Singapore
  • M.Sc. National University of Singapore
  • Ph.D. University of Sheffield, UK

We employ a variety of interdisciplinary techniques in our research, including molecular genetics, site-specific mutagenesis, protein purification, various spectroscopic methods and structural biology. Current research projects include:

1. Steroid degradation in Mycobacterium tuberculosis and other bacteria.
One third of the World's population is infected with Mycobacterium tuberculosis and about 10% of these individuals will develop tuberculosis during their lifetime. The emergence of drug resistant strains of M. tuberculosis, including the recent report of individuals infected with TDR-TB (totally drug resistant M. tuberculosis), has raised concerns that the currently used antibiotics may be insufficient to contain the disease. The cholesterol degradation pathway in M. tuberculosis is important for the persistence of the bacteria in host macrophages, and it therefore represents a potential target for development of new antibiotics against this pathogen.

2. Study of microbial enzymes involved in degradation of plant biomass (Lignin), aromatic environmental pollutants and mycotoxins.

1. Stirling, A.J., Gilbert, S.E., Conner, M., Mallette, E., Kimber, M.S., Seah S.Y.K. (2020) A key glycine in bacterial steroid-degrading acyl-CoA dehydrogenases allows Flavin-ring repositioning and modulates substrate side chain specificity. Biochemistry 59:4081-4092


2. Aggett R., Mallette, E., Gilbert, S.E., Vachon, M.A., Schroeter, K.L., Kimber, M.S. and Seah S.Y.K. (2019) The steroid side chain cleaving aldolase Ltp2-ChsH2DUF35 is a thiolase superfamily member with a radically repurposed active site.  J. Biol. Chem. 294:11934-11943.


3. Gilbert, S. Hood, L. and Seah, S.Y.K. (2017) Characterization of an aldolase involved in cholesterol side chain degradation in Mycobacterium tuberculosis. J. Bacteriol. 200: e00512-17


4. Mazurkewich, S., Brott, A.S., Kimber, M.S. and Seah S.Y.K. (2016) Structural and Kinetic Characterization of the 4-Carboxy-2-Hydroxymuconate Hydratase from the Gallate and Protocatechuate 4,5-Cleavage Pathways of Pseudomonas putida KT2440 J. Biol. Chem. 291:7669-7686.


5. Baker, P and Seah, S.Y.K. (2012) Rational Design of Stereoselectivity in the Class II Pyruvate Aldolase BphI. J Am Chem Soc. 134:507-513.


  • Nadine Abraham (Ph.D.)
  • Nicolas Rolfe (M.Sc.)
  • Edicon Chan (M.Sc.)
  • Avelene Kong