Strategies for Enhancing Microbial Production of 2'-Fucosyllactose, the Most Abundant Human Milk Oligosaccharide

Human milk oligosaccharides (HMOs), a group of structurally diverse unconjugated glycans in breast milk, act as important prebiotics and have plenty of unique health effects for growing infants. 2 '-Fucosyllactose (2 '-FL) is the most abundant HMO, accounting for approximately 30%, among approximately 200 identified HMOs with different structures. 2 '-FL can be enzymatically produced by alpha 1,2-fucosyltransferase, using GDP-L-fucose as donor and lactose as acceptor. Metabolic engineering strategies have been widely used for enhancement of GDP-L-fucose supply and microbial production of 2 '-FL with high productivity. GDP-L-fucose supply can be enhanced by two main pathways, including de novo and salvage pathways. 2 '-FL-producing alpha 1,2-fucosyltransferases have widely been identified from various microorganisms. Metabolic pathways for 2 '-FL synthesis can be basically constructed by enhancing GDP-L-fucose supply and introducing alpha 1,2-fucosyltransferase. Various strategies have been attempted to enhance 2 '-FL production, such as acceptor enhancement, donor enhancement, and improvement of the functional expression of alpha 1,2-fucosyltransferase. In this review, current progress in GDP-L-fucose synthesis and bacterial alpha 1,2-fucosyltransferases is described in detail, various metabolic engineering strategies for enhancing 2 '-FL production are comprehensively reviewed, and future research focuses in biotechnological production of 2 '-FL are suggested.