Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis

Abstract

The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics.

Keywords: Antiadhesive; Antimicrobial; Function; Human milk oligosaccharides (HMOS); Immunomodulator; Prebiotic; Structure; Synthesis.

FIG. 1.

One-pot multienzyme (OPME) GlcNAc (A), Gal (B), and Neu5Ac (C) activation and transfer systems.^, Enzyme abbreviations: BiNahK, B. infantis N-acetylhexosamine-1-kinase; PmGlmU, P. multocida N-acetylglucosamine 1-phosphate uridylyltransferase; PmPpA, P. multocida inorganic pyrophosphatase; GlcNAcT, N-acetylglucosaminyltransferase; NmLgtA, Neisseria meningitidis β1–3-N-acetylglucosaminyltransferase; EcGalK, E. coli K-12 galactose kinase; BLUSP: B. longum UDP-sugar synthase; GalT, galactosyltransferase; NmLgtB, Neisseria meningitidis β1–4-galactosyltransferase; NmCSS, Neisseria meningitidis CMP-sialic acid synthetase; SiaT, sialyltransferases; PmST1 M144D, Pasteurella multocida α2–3-sialyltransferase 1 M144D mutant; Pd2,6ST, Photobacterium damselae α2–6-sialyltransferase;^, CstII, Campylobacter jejuni α2–8-sialyltransferase II.^,

FIG. 2.

OPME and sequential OPME systems for the synthesis of disialyl oligosaccharides including DSLNnT, GD3 tetraose, DSLac, DS’LNT, and a monosialylpentaose LSTd (3”’-sLNnT). The structure of DSLNT found in human milk is shown for comparison purpose.