Structure, function, synthesis and improved strategies of fucosylated human milk oligosaccharides and their future perspectives: A review

Human milk oligosaccharides (HMOs) are a diverse group of lactose-derived carbohydrates and represent the third most abundant component in human milk. Fucosylated HMOs, which are particularly abundant, offer significant benefits to infants and have garnered increasing interest in recent decades. However, their widespread application in the food industry and other sectors remains limited due to challenges associated with their synthesis and isolation on a large scale. This review summarizes the chemical structures of fucosylated HMOs and their biological functions, critically evaluates conventional and cutting-edge synthetic strategies, and discusses the major challenges and future prospects in this field. Despite advancements, our understanding of the bioactivities and functions of fucosylated HMOs remains limited, necessitating further in vitro and in vivo studies. Fucosidase-catalyzed transfucosylation and metabolic engineering have emerged as promising strategies for their synthesis. Additionally, plant-based synthesis offers a sustainable alternative for large-scale production. Genetic modification, reaction condition optimization, and protein engineering have significantly improved the production of fucosylated HMOs. However, challenges such as identifying economical substrates, obtaining enzyme crystal structures for molecular engineering, developing advanced purification techniques, and ensuring the safety of synthesized products remain. Systematic evaluation and integration of knowledge are essential to drive progress in this field.