Research Projects

Human milk oligosaccharides, found in breast milk, are structurally diverse lactose-based oligosaccharides with significant health benefits. They protect infants from infectious diseases, aid in intestine and immune system maturation, and improve cognition. Fucosylated HMOs are crucial for gut colonization, protection from pathogens, and gut homeostasis. They are sought after for synthesis in infant formulae and supplements. The GH29A family of alpha-L-fucosidases are preferred for synthesis, but most studies use expensive synthetic substrates. A bioinformatics-based strategy is proposed to mine microbial diversity for relevant alpha-L-fucosidases, likely using xyloglucan or fucoidan as donor substrates. A smart fluorescence-based and lectin-based screen is used to identify transfucosylation linkages catalyzed. The study aims to biochemically characterize and compare microbial alpha-L-fucosidases for synthesis of fucosylated HMOs using xyloglucan or fucoidan. The proposal also includes detailed sequence/structural analysis, study of reaction conditions, and enzyme engineering to improve transfucosylation efficiency. Successful execution of this proposal will enable the synthesis of medically and industrially relevant fucosylated human milk oligosaccharides.