Advances on Biosynthesis of Human Milk Oligosaccharides.

Human milk oligosaccharides (HMOs), the third most abundant solid component in human milk, exert pivotal biological functions like gut microbiota modulation and immune regulation. This review details HMOs' discovery, classification, content dynamics, and core biological roles and then summarizes three generations of synthesis technologies - chemical/enzymatic/chemo-enzymatic synthesis, bacterial biosynthesis, and yeast-based biosynthesis - analyzing their respective merits and limitations. Furthermore, it discusses key challenges in HMO industrialization, including regulatory compliance, fermentation scale-up, medium optimization, and process automation, and highlights the latest global approval progress of biosynthetic HMO products. The review provides a comprehensive reference for the advancement of HMO biosynthesis technologies and their industrial translation.