Recent Progress on the <italic style="font-style: italic">in vitro</italic> Bio-transformation Synthesis of Human Milk Oligosaccharides

LI Yi; LI Yinshuang; LI Shuang; LING Peixue; FANG Junqiang

doi:10.12211/2096-8280.2025-052

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Recent Progress on the in vitro Bio-transformation Synthesis of Human Milk Oligosaccharides

更新时间：2025-07-30

- Recent Progress on the in vitro Bio-transformation Synthesis of Human Milk Oligosaccharides
- Synthetic Biology Journal Pages: 1-16(2025)
- 作者机构：
  
  山东大学，国家糖工程技术研究中心，山东青岛 266237
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-052
  CLC： Q81
- Received：29 May 2025，
  
  Revised：2025-07-29，
  
  Online First：30 July 2025，
- 稿件说明：
移动端阅览
李毅，李因双，李爽，凌沛学，房俊强. 人乳寡糖的体外生物转化合成研究进展［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-052

LI Yi， LI Yinshuang， LI Shuang， LING Peixue， FANG Junqiang. Recent Progress on the in vitro Bio-transformation Synthesis of Human Milk Oligosaccharides［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-052
李毅，李因双，李爽，凌沛学，房俊强. 人乳寡糖的体外生物转化合成研究进展［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-052 DOI：

LI Yi， LI Yinshuang， LI Shuang， LING Peixue， FANG Junqiang. Recent Progress on the in vitro Bio-transformation Synthesis of Human Milk Oligosaccharides［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-052 DOI：

摘要

人乳寡糖是存在于人乳中的天然活性寡糖，对新生儿健康至关重要。人乳寡糖具有多种健康益处，如益生元活性、抗炎和抗菌特性、抗病毒以及促进新生儿认知发展作用等，已经成为婴儿配方奶粉、临床婴儿营养品、膳食补充剂或功能食品的重要组分。随着越来越多人乳寡糖获批应用于婴儿配方奶粉，其在商业领域的价值愈发凸显，人乳寡糖规模化制备技术也成为研究热点。鉴于人乳寡糖广阔的应用前景与市场需求，以及体外生物转化（ivBT）在大宗糖类产品生产中展现的高效、绿色、可规模化放大等显著优势，本文综述了人乳寡糖的结构组成、功能特性和合成方法，尤其是体外生物转化在人乳寡糖规模制备领域的研究进展，为相关基础研究与产业转化提供理论依据与技术参考。未来ivBT将向原料绿色化、酶元件改造智能化、过程连续化纵深发展，进一步降低人乳寡糖高效规模化生产的综合成本，为产业化注入新动能。

Abstract

Human milk oligosaccharides (HMOs) are naturally occurring bioactive oligosaccharides existed in human milk

playing a critical role in neonatal health. These oligosaccharides confer multiple health benefits

including prebiotic activity

anti-inflammatory effects

antimicrobial activity

and antiviral properties

as well as the promotion of cognitive development in newborns. Consequently

HMOs have emerged as essential components in infant formula

clinical nutrition products

dietary supplements

and functional foods. The escalating commercial value of HMOs has driven intensive research into scalable production technologies. Traditional extraction and chemical synthesis methods for HMOs face challenges such as low efficiency

high costs

and limited yields. Accordingly

biotechnological approaches leveraging metabolic engineering and enzyme catalysis have become mainstream strategies for HMOs production. Although metabolic engineering of microbial strains improves HMOs yields and lowers production costs

challenges including inefficient substrate transport

byproduct accumulation

and product purification hurdles remain unresolved.

In vitro

Bio-Transformation (ivBT) integrates the advantages of enzymatic catalysis and microbial fermentation

enabling efficient extracellular biosynthesis and has emerged as an innovative biomanufacturing strategy. This approac

h addresses bottlenecks in traditional microbial synthesis

including low substrate utilization efficiency and byproduct formation—through enzyme discovery

pathway reconstruction

and optimization of reaction systems. Through enzyme engineering for novel substrate specificity and de novo multienzyme pathway design

ivBT enhances both product purity and yield while reducing complexity and costs

thereby providing novel methodologies for scalable HMOs synthesis.This paper reviews the structure

functional properties

and synthesis methods of human milk oligosaccharides

with a focus on the research progress of ivBT in the large-scale preparation of HMOs. It highlights the recent advances in ivBT technology

particularly in enzyme discovery and engineering

the construction of

in vitro

multi-enzyme catalytic pathways

and the scaling up of reaction systems. Furthermore

it analyzes the challenges and future trends of ivBT in the industrial production of HMOs

aiming to provide a theoretical basis and technical reference for related basic research and industrial transformation.

关键词

Keywords

references

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Enzymatic synthesis of 2'-fucosyllactose： advances and perspectives

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SHI Ran

JIANG Zhengqiang

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College of Food Science and Nutritional Engineering， China Agricultural University

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Recent Progress on the in vitro Bio-transformation Synthesis of Human Milk Oligosaccharides

DOI：10.12211/2096-8280.2025-052

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