Recent Technology Development for the Biosynthesis of Human Milk Oligosaccharide

Background: Human milk oligosaccharide (HMO) is a third most abundant component in breast milk. HMOs are molecules naturally tailored to the need of an infant. They protect infants from diseases, foster healthy gastrointestinal systems, reinforce fledgling immune function, and promote early brain development. Supplement HMOs to infant formula, which lack this critical element, would substantially improve the function of formula. Overwhelming evidence also indicate that HMOs can be used for the treatment of arthritis and related autoimmune disease, and inhibition of bacteria adhesion or as potential prebiotics. The prospect of using HMO in these applications has stimulated worldwide interest in developing synthesis technology for these valuable products. Methods: As the quantities extracted from human milk are limited, and chemical synthesis methods are time-consuming, costly, and complex, biotechnological approach, involving either enzyme catalysis or metabolically engineered bacteria is preferred. In this review, we highlight the most recent advances in the synthesis technologies, as disclosed in patents and patent applications, and analyze these technologies against those reported in literatures. Conclusion: Significant progress has been made over the past decade, especially in whole-cell biocatalysis for smaller HMOs. Significant challenges remain for larger and more complex HMOs. Keywords: Human milk oligosaccharide, prebiotics, glycosyltransferases, glycosidases, microbial fermentation, metabolic engineering.