关键词: 合成生物学, 3'-唾液酸乳糖, 生物合成, 唾液酸乳糖, 6'-唾液酸乳糖

Abstract:

Human Milk Oligosaccharides (HMOs) stand as a pivotal bioactive component in human milk, playing an irreplaceable role in infant health. As the third most abundant solid constituent, they range from 5 to 15 g/L, trailing only lactose and fat. Their multifaceted functions form a robust defense system for infants: by fostering the colonization of beneficial bacteria like bifidobacteria, they maintain a healthy intestinal microecology, while simultaneously inhibiting pathogen adhesion to safeguard the gut barrier. Beyond the gut, HMOs directly modulate immune system development, significantly boosting infants' anti-infection capabilities. Chemically, HMOs are categorized into neutral and acidic oligosaccharides, with sialylated human milk oligosaccharides (SHMOs) emerging as a standout subgroup. These complex carbohydrates, rich in sialic acid residues, are particularly concentrated in colostrum, underscoring their critical role in early infant development. Among SHMOs, 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) have garnered extensive research attention, in addition to more complex human milk oligosaccharides, such as LSTc, sialic acid lactose-N-tetrasaccharide a (LSTa), and disialic acid lactose-N-tetrasaccharide (DLSNT), among others.. Notably, 3'-SL and 6'-SL have achieved GRAS status from the FDA, enabling their inclusion in infant formulas and dietary supplements. The synthesis of SL involves diverse approaches, including chemical synthesis, enzymatic catalysis, and microbial fermentation. Chemical methods, while straightforward, often face challenges like low specificity and environmental concerns. Enzymatic synthesis, leveraging sialyltransferases, offers higher selectivity but struggles with cost and scalability. Microbial fermentation, powered by metabolic engineering, shows promise for large-scale production but requires optimization of biosynthetic pathways to enhance efficiency. In terms of applications, SL's versatility shines across multiple domains. In infant nutrition, it mimics the natural benefits of breast milk, supporting gut health and immune development. In pharmaceuticals, its antiviral properties—by blocking pathogen entry into host cells—and anti-inflammatory effects position it as a potential therapeutic agent. Additionally, emerging research highlights its role in neurodevelopment, as sialic acid residues contribute to brain growth and cognitive function. Despite these advancements, large-scale SL production faces hurdles: low synthesis yields, complex purification processes, and high production costs. Future breakthroughs are expected to stem from synthetic biology and metabolic engineering, with efforts focused on optimizing microbial strains, streamlining pathways, and developing cost-effective purification techniques. These innovations will pave the way for SL's broader application in infant nutrition, functional foods, and pharmaceutical development, unlocking its full potential as a transformative bioactive molecule.

Key words: synthetic biology, 3'-sialyllactose, sialyllactose, biosynthesis, 6'-sialyllactose