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

摘要：

母乳低聚糖（Human Milk Oligosaccharides，HMOs）是母乳中仅次于乳糖和脂肪的第三大固体成分，其含量可达到5-15g/L，对婴儿的生长发育有着至关重要的作用。HMOs不仅能促进婴儿肠道中有益菌群（如双歧杆菌）的定植，抑制病原体附着，还能直接调节免疫系统发育，增强抗感染能力。根据其化学结构，HMOs可分为中性低聚糖（如2'-岩藻糖基乳糖）和酸性低聚糖两大类，唾液酸化的HMOs是其主要成分之一，并且唾液酸化人乳低聚糖（SHMOs）是一类含有唾液酸残基的复杂碳水化合物，在母乳中含量丰富，尤其在初乳中占比更高。常见的SHMOs 包括结构相对简单的3'-唾液酸乳糖（3'-sialyllactose，3'-SL）和6'-唾液酸乳糖（6'-sialyllactose，6'-SL），以及更复杂的人乳寡糖LSTc、唾液酸乳糖-N-四糖a（LSTa）、双唾液酸乳糖-N-四糖（DLSNT）等。其中3'-SL和6'-SL是唾液酸乳糖（sialyllactose，SL）中研究最多且功能较为明确的两种形式，目前已经获得了美国食品和药物管理局（FDA）的公认安全（GRAS）批准，可以添加到婴儿配方奶粉或者其它膳食中。本文重点介绍了HMOs的分类、SL的合成方法、功能与应用，并鉴于目前SL合成以及应用情况，提出了当前所面临的挑战和未来方向。SL不仅能够调节肠道菌群平衡，还具有抗炎、抗病毒及促进神经发育等作用，因此在医药、食品和营养补充剂等领域展现出巨大潜力。然而，SL的大规模生产仍面临诸多挑战，如合成效率低、纯化工艺复杂等。未来，随着合成生物学和代谢工程技术的发展，优化SHMOs的生物合成途径、提高产量并降低成本将成为重要研究方向，以推动其在婴幼儿营养、功能性食品及药物开发中的广泛应用。

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