Advances and Challenges of 2′-Fucosyllactose: Physiological Function and Biotechnological Production

As essential prebiotics in breast milk, human milk oligosaccharides (HMOs) are critical for infant health including guiding the development of the gut microbiota, fine-tuning immune responses, and strengthening the intestinal barrier. These functions support the potential of HMOs to confer health benefits in adults as well. 2'-Fucosyllactose (2'-FL), a major trisaccharide in human milk, is a well-tolerated infant nutrient that is approved as a novel food in many countries. To date, 2'-FL can be efficiently synthesized by various cell factories via <i>de novo</i> and salvage pathways. Key strategies for increasing the 2'-FL titer include enhancing the GDP-l-fucose supply, introducing highly active α1,2-fucosyltransferases, and using diverse carbon sources to expand production flexibility. This review explores the health benefits of 2'-FL, along with key advances in the engineering of microbial cell factories and α1,2-fucosyltransferases for its production, concluding with a forward-looking perspective on priority research areas for enhancing its application.