Research progress on biosynthesis of human milk oligosaccharides

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Research progress on biosynthesis of human milk oligosaccharides

更新时间：2025-07-28

- Research progress on biosynthesis of human milk oligosaccharides
- Synthetic Biology Journal Pages: 1-16(2025)
- 作者机构：
  
  1.江南大学食品学院，食品科学与资源挖掘全国重点实验室，江苏无锡 214122
  2.江南大学生物工程学院，江苏无锡 214122
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-047
  CLC：
- Received：20 May 2025，
  
  Revised：2025-07-21，
  
  Online First：28 July 2025，
- 稿件说明：
移动端阅览
万李，杨龙浩，罗国聪，朱莺莺，沐万孟. 母乳低聚糖生物合成研究进展［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-047

WAN Li， YANG Longhao， LUO Guocong， ZHU Yingying， MU Wanmeng. Research progress on biosynthesis of human milk oligosaccharides［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-047
万李，杨龙浩，罗国聪，朱莺莺，沐万孟. 母乳低聚糖生物合成研究进展［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-047 DOI：

WAN Li， YANG Longhao， LUO Guocong， ZHU Yingying， MU Wanmeng. Research progress on biosynthesis of human milk oligosaccharides［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-047 DOI：

摘要

母乳低聚糖（Human milk oligosaccharides，HMOs）是母乳中的核心营养成分，对于婴幼儿的生长发育具有无可替代的生理功效，是新一代婴幼儿配发奶粉的核心原料。目前针对HMOs的研究主要集中在生理功能、临床应用以及生物合成技术开发等方面。鉴于HMOs广阔的市场需求，高效生物合成HMOs逐渐成为研究热点。合成生物学技术的突破使微生物发酵法大规模生产HMOs成为可能，显著提升了产业化进程的经济可行性。本文系统综述近年来HMOs的研究进展并展望了HMOs的发展趋势及挑战，包括：（1）HMOs相关生理功能研究进展；（2）HMOs生物合成关键糖基转移酶研究进展；（3）基于微生物细胞工厂的HMOs生物合成路径设计；（4）用于改造HMOs合成底盘细胞的合成生物学策略。通过解析HMOs生物合成关键酶元件筛选、代谢途径通量平衡及底盘细胞代谢网络调控等核心科学问题，为HMOs的高效生物制造提供理论依据与技术参考。

Abstract

Human milk oligosaccharides (HMOs)

recognized as key bioactive constituents of human milk

play indispensable roles in infant growth and development through immunomodulation

gut microbiota regulation

and pathogen defense mechanisms. These multifaceted compounds have emerged as pivotal ingredients in next-generation infant formula formulations. Current investigations primarily concentrate on three domains: elucidation of biological functions

exploration of therapeutic applications

and optimization of biosynthesis platforms. The growing commercial demand for HMOs has driven significant advancements in enzymatic synthesis and metabolic engineering approaches to achieve cost-effective production at industrial scales. The rapid development of synthetic biology has revolutionized the production of HMOs

making large-scale microbial fermentation a viable and economically feasible strategy for industrial applications. This paradigm shift has significantly accelerated the commercialization of HMOs

which are increasingly recognized for their critical roles in infant nutrition

gut microbiota modulation

and immune system development. In this comprehensive review

we systematically evaluate the latest research progress in HMOs

with particular emphasis on their biosynthesis

functional mechanisms

and biotechnological production

focusing on four key dimensions: (1) Physiological functions and mechanistic insights of HMOs-recent studies have elucidated the prebiotic

antimicrobial

and immunomodulatory properties of HMOs

highlighting their structural diversity and structure-function relationships. Advances in glycomics and microbiome research have deepened our understanding of how HMOs influence host-microbe interactions and metabolic pathways. (2) Discovery and engineering of glycosyltransferases for HMOs biosynthesis-glycosyltransferases (GTs) play a pivotal role in determining the structural diversity of HMOs. We review the latest strategies for enzyme mining

characterization

and protein engineering

including directed evolution and computational design

to enhance catalytic efficiency and substrate specificity. (3) Metabolic pathway design and optimization in microbial cell factories–the construction of efficient microbial chassis for HMOs production requires systematic pathway engineering. Key considerations include precursor supply

cofactor balancing

and the elimination of metabolic bottlenecks. We discuss recent advances in dynamic pathway regulation and modular assembly techniques to improve yield and purity. (4) Synthetic biology strategies for chassis cell development–the optimization of host strains involves genome-scale metabolic modeling

CRISPR-based genome editing

and adaptive laboratory evolution. Additionally

novel approaches such as cell-free biosynthesis and consortia-based fermentation are emerging as promising alternatives for complex HMOs synthesis. Furthermore

we discuss emerging challenges and future directions in this field.

2

关键词

Keywords

references

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