Abstract

Human milk oligosaccharides (HMOs) have recently attracted ever-increasing interest because of their versatile physiological functions. In HMOs, two tetrasaccharides, lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), constitute the essential components, each accounting 6% (w/w) of total HMOs. Also, they serve as core structures for fucosylation and sialylation, generating functional derivatives and elongation generating longer chains of core structures. LNT, LNnT, and their fucosylated and/or sialylated derivatives account for more than 30% (w/w) of total HMOs. For derivatization, LNT and LNnT can be modified into a series of complex fucosylated and/or sialylated HMOs by transferring fucose residues at α1,2-, α1,3-, and α1,3/4-linkage and/or sialic acid residues at α2,3- and α2,6-linkage. Such structural diversity allows these HMOs to possess great commercial value and an application potential in the food and pharmaceutical industries. In this review, we first elaborate the physiological functions of these tetrasaccharides and derivatives. Next, we extensively review recent developments in the biosynthesis of LNT, LNnT, and their derivatives in vitro and in vivo by employing advanced enzymatic reaction systems and metabolic engineering strategies. Finally, future perspectives in the synthesis of these HMOs using enzymatic and metabolic engineering approaches are presented.

摘要

人乳寡糖 (HMOs) 最近因其多种生理功能而引起了越来越多的关注。在 HMOs 中，两种四糖，即乳-N-四糖(LNT) 和乳-N-新四糖(LNnT) 构成基本成分，各占总 HMOs 的 6% (w/w)。此外，它们作为岩藻糖基化和唾液酸化的核心结构，产生功能衍生物和延伸产生更长的核心结构链。LNT、LNnT 及其岩藻糖基化和/或唾液酸化衍生物占总 HMO 的 30% 以上 (w/w)。对于衍生化，LNT 和 LNnT 可以通过转移α 1,2-、α 1,3- 和α 1,3/4-键和/或唾液酸残基在α 2,3- 和α 2,6-键。这种结构多样性使这些HMOs在食品和制药行业具有巨大的商业价值和应用潜力。在这篇综述中，我们首先阐述了这些四糖及其衍生物的生理功能。接下来，我们通过采用先进的酶促反应系统和代谢工程策略，广泛回顾了 LNT、LNnT 及其衍生物在体外和体内生物合成的最新进展。最后，提出了使用酶和代谢工程方法合成这些 HMO 的未来前景。