Research

We are interested in structure-function relationships of enzymes and enzyme evolution i.e. the relationship between sequence/structural homology and function. Many of the enzymes we work with also form heteromeric complexes and are ideal candidates for investigating how quaternary structures and  protein-protein interactions modulate the functions of biological catalysts.

​Projects in our lab include

(1) Steroid degradation by Mycobacterium tuberculosis and related bacteria

Steroids are present in animals, plants, and fungi, where they serve diverse roles, including modulating membrane fluidity and functioning as hormones that regulate an organism’s physiology, growth, and development. Although most bacteria do not synthesize steroids, many can chemically modify them and even use steroids as carbon and energy sources for growth. This microbial capacity for steroid transformation is relevant to the pathogenesis of certain bacteria, plays an important role in gut health, and can also be leveraged for the biotechnological production of steroid pharmaceuticals.

For example, the cholesterol degradation pathway in Mycobacterium 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 the  pathogen that causes tuberculosis. ile acids, a class of steroids secreted into the intestine to facilitate the emulsification, digestion, and absorption of dietary fats, can be modified by intestinal bacteria. These microbial transformations generate metabolites that have been implicated in the development of gallstones, liver cancer, and inflammatory bowel diseases. Finally, many steroid-based pharmaceuticals used to treat a range of human diseases, including asthma and inflammatory conditions, rely on microbial transformation of natural steroids to generate intermediates that can then be chemically modified to produce the final drugs. A deeper understanding of these microbial processes would improve our ability to combat steroid-related diseases and to harness microbial metabolism for therapeutic drugs development.

Our lab is investigating a variety of enzymes involved in sterol and bile acid transformation, with the goal of defining their structure–function relationships. We aim to understand how these enzymes selectively recognize and bind these bulky and structurally complex steroidal molecules.

(2) Lignin/ Aromatic Pollutants and toxins Degradation
We study enzymes involved in aromatic/cyclic hydrocarbon and toxin degradation. In the PCBs degradation pathway, the aldolase, BphI, is in complex with a dehydrogenase, BphJ, that catalyze the transformation of the aldehyde product from the aldolase reaction to acyl CoAs. Aldehyde products, of various lengths and subsitution, are channeled from the aldolase to the dehydrogenase via a molecular tunnel, ensuring that the toxic aldehydes do not poison the cells. We are investigating how vectorial movements of aldehydes through the enzyme complex are accomplished through protein dynamics using combination of biochemical and structural approaches.

(3) Detoxification of mycotoxins

In collaboration with Dr. Ting Zhou at Agriculture Agri-food Canada, we are isolating and characterizing microbial enzymes capable of detoxifying the mycotoxins, deoxynivalenol and patulin. These mycotoxins contaminate grains and fruit juices, posing serious health risks to humans and livestock, while also causing substantial economic losses in agriculture and food production.

Our laboratory is situated at the Science complex providing us with access to state-of-the-art facilities and instruments.

We employ a wide variety of interdisplinary techniques in our research, including

Recent Selected Publications

Rolfe N, Myskiw D, Patton MT, Forrester TJB, Kimber MS, Seah SYK. (2025) Sad from Proteobacteria is a structurally distinct ALDH3 enzyme specialized for the oxidation of steroidal aldehydes. Biochemistry 64:3735-3744.

Rolfe N, Schroeter KL, Forrester TJ, Kimber MS, Seah SYK. (2025) Sal is a proteobacterial bile acid aldolase that repurposes key thiolase catalytic residues for retroaldol cleavage of C₅ steroid side chains. J Biol Chem. 301:110439.  

Yang C, Huang L, Huang K, Seah SYK, Peng B. (2025) Effects of patulin stress on the physiology, fermentation performance, and aroma profile of Saccharomyces cerevisiae during fermentation. J Food Sci. 90:e70248.

. Yang, C, Huang, L, Hu, C, Yao, J, Zhou, T, Li, XZ, Seah, SYK. and Peng, B. (2025) Identification and characterization of aldo-keto reductase responsible for patulin degradation in Saccharomyces cerevisiae. Food Chemistry 478, 143706.

Abraham, N., Chan, E., Li, XZ, Zhu H, Mats L, Zhou T AND Seah SYK. (2025) Patulin Detoxification by Evolutionarily Divergent Reductases of Gluconobacter oxydans ATCC 621. J Agric Food Chem. 73:6842-6853.

Schroeter KL, Rolfe N, Forrester TJB, Kimber MS, Seah SYK (2024) Shy is a proteobacterial steroid hydratase which catalyzes steroid side chain degradation without requiring a catalytically inert partner domain. J Biol Chem. 300:107509.

Abraham, N, Chan, E.T.S., Zhou, T. and Seah, S.Y.K. (2022) Microbial detoxification of mycotoxins in food. Frontiers in Microbiology 13:957148

Abraham, N, Schroeter, K.L., Zhu, Y., Chan, J., Evans, N., Kimber, M.S., Carere, J., Zhou, T. and Seah, S.Y.K. (2022) Structure-function characterization of an aldo-keto reductase involved in detoxification of the mycotoxin, deoxynivalenol. Scientific Reports 12:14737.

Schroeter, K.L., Abraham, N., Rolfe, N., Barnshaw, R., Diamond, J. and Seah, S.Y.K. (2022) Bacterial hydratases involved in steroid side-chain degradation have distinct substrate specificities. J. Bacteriol. 204:e0023622

Chan E.T.S., Zhu, Y., Li, X.Z., Zhou, T. and Seah S.Y.K. (2022) Characterization of two dehydrogenases from Gluconobacter oxydans Involved in the transformation of patulin to ascladiol. Toxins (Basel) 14:423

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