Employment of fucosidases for the synthesis of fucosylated oligosaccharides with biological potential

Abstract

Fucosylated oligosaccharides play important physiological roles in humans, including in the immune response, transduction of signals, early embryogenesis and development, growth regulation, apoptosis, pathogen adhesion, and so on. Efforts have been made to synthesize fucosylated oligosaccharides, as it is difficult to purify them from their natural sources, such as human milk, epithelial tissue, blood, and so on. Within the strategies for its in vitro synthesis, it is remarkable the employment of fucosidases, enzymes that normally cleave the fucosyl residue from the non-reducing end of fucosylated compounds, as these enzymes are also capable of synthesizing them by means of a transfucosylation reaction. This review summarizes the progress in the use of fucosidases for the synthesis of compounds that have potential for industrial and commercial applications.

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

“…By comparison, the fucosyl donor for 2′-FL biosynthesis by α1,2-fucosyltransferase, GDP- l -fucose, is a typical sugar nucleotide widely present in bacteria, of which the supply is easily strengthened by metabolic engineering approaches (Figure ), and further introduction of the 2′-FL-producing α1,2-fucosyltransferase is able to realize highly efficient synthesis of 2′-FL . The HMO-producing l -fucosidases, including α1,2- l -fucosidases, have been reviewed in detail before. ,, In this work, we only reviewed the 2′-FL biosynthesis by α1,2-fucosyltransferase (Table ), especially via metabolic engineering approaches.…”

“…4 The HMO-producing Lfucosidases, including α1,2-L-fucosidases, have been reviewed in detail before. 42,46,47 In this work, we only reviewed the 2′-FL biosynthesis by α1,2-fucosyltransferase (Table 1), especially via metabolic engineering approaches.…”

α-L-Fucosidases from an Alpaca Faeces Metagenome: Characterisation of Hydrolytic and Transfucosylation Potential

“…Therefore, the ability to generate fucosylated saccharide analogues shows the potential to create compounds like those found in HMOs. Other researchers employ α-L-fucosidases for the synthesis of various fucosylated glycosides, such as fucosyllactose [24], lacto-N-fucopentaose [22], and their analogues [18,48]. BF0028 α-L-fucosidase from B. fragilis, which is related to Fuc25A, Fuc25D, and Fuc25E (Figure 1), could not perform transfucosylation reaction with glucose, maltose, lactose, galactose, and fructose as fucosyl acceptors.…”

Computer Simulation to Rationalize “Rational” Engineering of Glycoside Hydrolases and Glycosyltransferases

“…Retaining GHs can be engineered for synthetic purposes by limiting their innate hydrolytic activity to favor their  usually secondary  transglycosylation activity. In this case, a carbohydrate acceptor rather than a water molecule reacts with the enzyme during the second reaction step (Scheme a). , Several strategies have been tested for this purpose, and enzyme variants have been developed that significantly increase the synthetic yields, ,, but the most successful engineering strategy to date for GHs is the glycosynthase approach (Scheme b), , a rational design approach based on the modification of the enzyme mechanism combined with the use of artificial substrates. In glycosynthases, the nucleophilic residue of a retaining GH is mutated into a catalytically impotent residue, while the mutant enzyme is supplied with an activated donor residue of opposite anomeric configuration compared to the native enzyme.…”