Strategies for synthesizing human milk lacto-N-fucopentaoses oligosaccharides

Lacto-N-fucopentaoses (LNFPs) of type I to V are representative components of human milk oligosaccharides (HMOs) and have garnered increasing attention due to their multi-functional activities. These activities include regulating intestinal flora, resisting pathogen adhesion, and promoting the development and repair of the nervous system. Due to the limited resource of HMOs, artificial synthesis of HMOs can provide an alternative pathway to circumvent this limitation. Currently, LNFPs can be produced using various methods, including biosynthesis, chemical synthesis, and enzymatic synthesis. Currently, emphasis is placed on the last two methods. Chemical synthesis-based methods typically involve strict reaction conditions, cumbersome steps, and low yields. On the other hand, enzymatic synthesis offers several advantages, including mild reaction conditions, high yield, and good selectivity. However, only a few reports have focused on in vivo fermentation as a means to produce LNFPs, despite its cost advantage. In vivo fermentation presents an opportunity to supply the key substrates for fucosyl transfer reactions, namely LNnT and GDP-Fuc, along with the required biosynthesis enzymes. Further exploration of this approach is warranted.This paper aims to review the synthesis methods of LNFPs, their functional activities, and emerging trends in their development. By evaluating the different synthesis approaches, this review seeks to contribute to the advancement of LNFPs production and utilization