Biosynthesis of human milk oligosaccharides via metabolic engineering approaches: current advances and challenges

Human milk oligosaccharides (HMOs) are structurally complex unconjugated glycans that are the third largest solid component in human milk. HMOs have drawn increasing attention because of their beneficial effects to infant health. Of the more than 200 HMOs, only less than 10 have been used in medical or food industries. Although HMO research has been becoming increasingly intensive and booming, the limited availability of HMOs still cannot meet the demand in health effect research and large-scale application. Therefore, efficient synthetic approaches and strategies for HMO production are urgently needed. The goal of this review is to highlight recent advances in microbial cell factory development for HMO biosynthesis. Key challenges in representative HMO production are also highlighted. The further perspectives in general HMO biosynthesis are discussed.