人乳寡糖2′-岩藻糖基乳糖的功能及其全细胞生物合成

Function and whole-cell biosynthesis of human milk oligosaccharide 2′-fucosyllactose

母乳是新生儿最理想的营养剂。其中,人乳寡糖作为母乳的第三大固体组分,对新生儿的生长、发育及健康状况有重要影响,被应用于婴幼儿配方食品中。2′-岩藻糖基乳糖(2′-fucosyllactose,2′-FL),是分泌型母乳中含量最高的人乳寡糖,约占人乳寡糖总量的30%,具有重要的营养和医学价值。2′-FL能够促进婴幼儿生长发育、提高其认知能力、增强免疫力、抗过敏、抗病毒,以及调节肠道菌群,是极具潜力的新型营养强化剂。但是,2′-FL来源于母乳,依靠分离、提取获得大量2′-FL并不现实,因此亟需进行人工合成。人工合成2′-FL的方法有3种,包括:化学合成法、酶催化合成法和全细胞生物合成法。全细胞生物合成法因其成本相对低廉,且易于规模化扩大,而引起了国内外的广泛关注和研究。目前,国外很多跨国公司均开始布局2′-FL的工业化生产和应用,而我国在该领域尚处于研发阶段,因此,了解和掌握2′-FL的合成方法对我国开展2′-FL规模化生产具有重要的意义。本文旨在介绍2′-FL的功能特性,系统阐述其全细胞生物合成的关键技术和最新进展,讨论了针对限速步骤进一步提高产量的策略,旨在为2′-FL的合成和商业化生产提供生物学依据,为今后开发接近母乳的婴幼儿配方奶粉奠定基础。

Breast milk is the ideal food for infants.As the third most abundant solid ingredients in breast milk,human milk oligosaccharides(HMOs)have an important impact on the growth,development and health of infants.A few HMOs have been used in infant formulas.Among them,2′-fucosyllactose(2′-FL)has the highest content and comprises 30%of the total HMOs in secretor milk.With high nutritional and medical values,2′-FL is regarded as a new type of food nutrition fortifier,and it boasts multiple functions such as growth promotion,cognition benefits,immune enhancement,anti-allergic activity,anti-viral activity,and intestinal flora regulation.However,originating from breast milk,2′-FL is unlikely to be obtained by separation.Thus,it is urgent to synthesize 2′-FL in artificial manners,which include chemical and enzymatic synthesis and whole-cell biosynthesis.Cost-effective and easy to scale up,whole-cell biosynthesis of 2′-FL has received worldwide attention.At present many foreign multinational companies have begun the industrial production and commercial application of 2′-FL,whereas the relevant work in China remains in research.Therefore,it is of great significance for China to master the synthesis method of 2′-FL.This paper aimed to review the functional characteristics of 2′-FL and systematically describe the key technologies and the latest progress in whole-cell biosynthesis.The strategies of rate-limiting steps to increase production were also discussed.We sought to provide a biological basis for the synthesis and commercial production of 2′-FL.Further,the paper facilitated the development of infant formulas close to human milk.