中性核心母乳寡糖生物合成的研究进展和发展趋势

刘丹; 王建宇; 江正强

doi:10.12211/2096-8280.2025-083

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中性核心母乳寡糖生物合成的研究进展和发展趋势

特约评述 | 更新时间：2025-11-12

- 中性核心母乳寡糖生物合成的研究进展和发展趋势
- Research progress and development trends in the biosynthesis of neutral core human milk oligosaccharides
- 合成生物学 2025年6卷第5期页码：1126-1144
- 作者机构：
  
  1.中国农业大学食品科学与营养工程学院，北京 100083
  2.中原食品实验室，河南漯河 462300
  3.中国农业大学工学院，北京 100083
- 作者简介：
  
  [ "刘丹（1995—），女，博士研究生。研究方向为食品生物技术。E-mail：liudan379@163.com" ]
  [ "江正强（1971—），男，教授，博士生导师。研究方向为酶工程等。E-mail：zhqjiang@cau.edu.cn" ]
- 基金信息：
  
  国家自然科学基金(32172159)
- DOI：10.12211/2096-8280.2025-083
  中图分类号： Q815
- 收稿：2025-08-04，
  
  修回：2025-09-16，
  
  纸质出版：2025-10-31
- 稿件说明：
移动端阅览
刘丹，王建宇，江正强. 中性核心母乳寡糖生物合成的研究进展和发展趋势［J］. 合成生物学， 2025， 6（5）： 1126-1144

LIU Dan， WANG Jianyu， JIANG Zhengqiang. Research progress and development trends in the biosynthesis of neutral core human milk oligosaccharides［J］. Synthetic Biology Journal， 2025， 6（5）： 1126-1144
刘丹，王建宇，江正强. 中性核心母乳寡糖生物合成的研究进展和发展趋势［J］. 合成生物学， 2025， 6（5）： 1126-1144 DOI： 10.12211/2096-8280.2025-083.

LIU Dan， WANG Jianyu， JIANG Zhengqiang. Research progress and development trends in the biosynthesis of neutral core human milk oligosaccharides［J］. Synthetic Biology Journal， 2025， 6（5）： 1126-1144 DOI： 10.12211/2096-8280.2025-083.

摘要

母乳寡糖（human milk oligosaccharide，HMO）是母乳中重要的功能和营养成分。其中，中性核心母乳寡糖（neutral core human milk oligosaccharide，ncHMO）主要包括乳糖-

-三糖（LNT Ⅱ）、乳糖-

-新四糖（LNnT）和乳糖-

-四糖（LNT），在婴幼儿健康发育过程中发挥着不可替代的生理作用。近年来，中性核心母乳寡糖的生物合成技术快速发展，其工业化生产从可能走向现实。本文综述了中性核心母乳寡糖的酶法和微生物细胞法合成研究现状，介绍了糖基转移酶和糖苷酶在酶法合成中性核心母乳寡糖的应用，讨论了糖基转移酶的催化特性、底盘细胞的种类及改造等关键因素对微生物细胞法合成中性核心母乳寡糖产量的影响，进一步对比了两种方法生物合成中性核心母乳寡糖的优缺点。目前，中性核心母乳寡糖的生物合成存在酶催化效率低、底盘细胞选择与适配性差、副产物多及内毒素污染等问题，需通过理性设计酶元件、优化安全底盘、动态调控代谢网络及强化发酵纯化工艺等策略协同攻关，有望实现母乳寡糖的低成本、高效绿色生产，为开发更具营养价值的婴幼儿健康食品提供核心支撑。

Abstract

Human milk oligosaccharides (HMOs) are essentially functional and nutritional components found in human milk. They can be primarily classified into fucosylated

neutral core

and sialylated HMOs. Lacto-

-triose Ⅱ (LNT Ⅱ)

lacto-

-neotetraose (LNnT)

and lacto-

-tetraose (LNT) are common neutral core human milk oligosaccharides (ncHMOs)

which can be extended to form longer-chain HMOs and play important roles in intestinal health. In recent years

the biosynthesis of ncHMOs has developed rapidly

and industrial-scale production is from theoretical possibility to practical reality. The synthesis approaches for ncHMOs include chemical synthesis

enzymatic synthesis

and microbial cell synthesis. As the rapid development in biotechnology

enzymatic and microbial cell synthesis have emerged as prominent methods in ncHMOs bios

ynthesis. Enzymatic synthesis is highly efficient

regioselective

and stereoselective. Currently

glycosyltransferases and glycoside hydrolases represent the two major types of enzymes used for biosynthesizing ncHMOs. Glycosidase-based enzymatic synthesis has demonstrated high conversion rates for LNT Ⅱ and LNnT production. However

the enzymatic synthesis of LNT is less efficient and requires further improvement. Notably

the production of LNnT and LNT typically relies on LNT Ⅱ as a key precursor

requiring a multi-step synthetic strategy. Microbial cell synthesis employs metabolic engineering to construct continuously synthetic pathways in microbial cells such as

Escherichia coli

and

Bacillus subtilis

. Knocking out genes in competitive pathway

optimizing genes expression

regenerating cofactors have significantly enhanced the yields of ncHMOs. The biosynthesis of ncHMOs faces several critical challenges

including the low activity and poor substrate specificity of key glycosyltransferases

such as β-1

-acetylglucosaminyltransferase and β-1

3-galactosyltransferase. Additionally

the transporters of LNT Ⅱ and LNnT are not clear in microbial cell. Furthermore

the yields of LNT Ⅱ should be substantially improved for industrial-scale production. Thus

it is important to overcome the interconnected limitations in enzyme engineering (particularly glycosyltransferase specificity and activity)

microbial cell modification (focusing on metabolic compatibility and pathway design)

and bioprocess optimization (through rational pathway redesign)

via

an integrated synthetic biology and fermentation engineering approach in the future. These strategies are essential for achieving efficient

cost-effective biosynthesis of ncHMO at industrial scale.

关键词

Keywords

references

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