Research

Life Sciences & Biotechnology

Title :

Biochemical characterization of the transfucosylation potential of microbial fucosidases for the synthesis of fucosylated human milk oligosaccharides

Area of research :

Life Sciences & Biotechnology

Focus area :

Biochemistry

Principal Investigator :

Dr. Ramya T.N. Chakravarthy, CSIR– Institute Of Microbial Technology (Imtech), Chandigarh

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

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.

Co-PI:

Dr. Srikrishna Subramanian, CSIR– Institute Of Microbial Technology (Imtech), Chandigarh-160036

Total Budget (INR):

53,81,337

Organizations involved