Enzymatic and Chemoenzymatic Synthesis of Human Milk Oligosaccharides (HMOS)

Abstract

Human milk oligosaccharides (HMOS) play important roles in promoting the growth of beneficial bacteria and inhibiting the colonization of pathogenic bacteria in intestines, modulating immune functions, providing nutrients for brain development, and preventing some diseases in infants. In order to obtain individual HMOS for biological studies and clinical testing, various synthetic methods have been developed for the production of HMOS. Here we summarize our recent efforts in synthesizing structurally defined HMOS using one-pot multienzyme (OPME) glycosylation methods. Other enzymatic and chemoenzymatic synthetic approaches for HMOS are also reviewed. These strategies allow the access to some HMOS and their analogs for a diverse array of studies including the development of HMOS-based therapeutics and/or nutraceuticals. On the other hand, identifying additional glycosyltransferases that can be expressed in large amounts with the desired substrate specificity combined with the strategic design of the synthetic route is a continuous task for highly efficient enzymatic and chemoenzymatic synthesis of HMOS at large scale and for accessing the remaining more complex HMOS structures.