糖质ivBT生物合成的核心元件及关键技术

裴彩霞; 李建军; 杜昱光

doi:10.12211/2096-8280.2025-064

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糖质ivBT生物合成的核心元件及关键技术

特约评述 | 更新时间：2025-08-13

- 糖质ivBT生物合成的核心元件及关键技术
- Core Elements and Key Technologies of ivBT-based Glycan Synthesis
- 合成生物学 2025年页码：1-19
- 作者机构：
  
  1.中国科学院过程工程研究所，生物药制备与递送全国重点实验室，北京 100190
  2.中国科学院过程工程研究所，国家生化工程技术研究中心（北京），北京 100190
- 作者简介：
  
  [ "裴彩霞（1994—），女，博士，博士后，研究方向为功能寡糖的酶催化合成等研究。E-mail：peicaixia@ipe.ac.cn" ]
  [ "李建军（1970—），男，博士，副研究员，硕士生导师，研究方向为蛋白质工程、功能寡糖的酶催化合成等研究。E-mail：jjli@ipe.ac.cn" ]
  [ "杜昱光（1963—），男，硕士，研究员，博士生导师，研究方向为功能寡糖的制备、活性评估与产业化等研究。E-mail：ygdu@ipe.ac.cn" ]
- 基金信息：
  
  国家自然科学基金项目(21877114)
- DOI：10.12211/2096-8280.2025-064
  中图分类号： Q814.9
- 收稿：2025-06-23，
  
  修回：2025-08-10，
  
  网络首发：2025-08-13，
- 稿件说明：
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裴彩霞，李建军，杜昱光. 糖质ivBT生物合成的核心元件及关键技术［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-064

PEI Caixia， LI Jianjun， DU Yuguang. Core Elements and Key Technologies of ivBT-based Glycan Synthesis［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-064
裴彩霞，李建军，杜昱光. 糖质ivBT生物合成的核心元件及关键技术［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-064 DOI：

PEI Caixia， LI Jianjun， DU Yuguang. Core Elements and Key Technologies of ivBT-based Glycan Synthesis［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-064 DOI：

摘要

糖质（glycans）是构成生命的基本生物分子，在生物过程中发挥重要作用，与人类健康和疾病密切相关。由于糖质结构的复杂性，糖质所携带的密码信息大大超过核酸及蛋白质等任何其它生物大分子。为了破译糖质携带的密码信息，就需要获得一定量的、结构明确的糖质。合成仍然是获得糖质的最佳方式。体外生物转化（

in vitro

biotransformation， ivBT）是一个基于体外多酶催化的新型工业生物制造技术，由酶、辅酶等元件体外重构生化反应途径，实现目标产物的高效合成，正逐渐发展成为合成糖质的一种重要技术。本文综述了ivBT在糖质合成中的应用、ivBT糖质合成相关的糖核苷合成、糖基转移、NTP再生等核心元件及酶的固定化、微流控、酶促自动化合成、动力学模拟、离子液体等关键技术，展望了糖质ivBT合成相关的酶的协同性、特殊重组酶生产成本的降低、仿生辅酶的循环再生、多酶复合体的应用、硫酸化糖质的合成、AI辅助的反应条件优化等发展方向，旨在为糖质ivBT合成的未来发展提供指导。

Abstract

Glycans are the fundamental biomolecules that make up life and play important roles in biological processes

including cell growth and proliferation

immune responses

angiogenesis and tumor cell metastasis

toxin interaction

protein folding and degradation

cell-cell communications

and cell-pathogen interactions

and are closely related to human health and disease such as occurrence

development

and metastasis of tumor

inflammation

viral or bacterial infections

etc. Due to their structural complexity arising from the number of chemically similar (and often isomeric) monosaccharide building blocks

the position and orientation of glycosidic linkages

branching

and non-template-driven biosynthesis

the coding information they carry far exceeds that of any other biological macromolecules such as nucleic acids and proteins

which are generally linear structures and biosynthesized based on templates. To decipher the code information carried by glycans

it is necessary to obtain some structurally defined pure glycans. Since it is not possible to separate and purify glycans with defined structures from natural environment

synthesis remains the best approach to obtaining glycans. In vitro biotransformation (ivBT)

a novel industrial biomanufacturing platform based on multi-enzyme catalysis in vitro

has become an essential approach to obtain high value-added products due to its appealing advantages in rapid construction of nonnatural enzymatic pathways

higher product yields

faster reaction rates

and better tolerances to toxic compounds. ivBT is gradually being developed into an important means of glycan synthesis. This article reviews application of ivBT in glycan synthesis

the core elements such as synthesis of sugar-nucleotides

glycosyl transfer and NTP regeneration

and key technologies of ivBT-based glycan synthesis like enzyme immobilization

microfluidics

enzyme-mediated automatic synthesis

dynamic simulation

and ion liquids

aiming to provide guidance for its future development

including synergism of multi-enzyme

reduction of production costs for special recombinant enzymes

regeneration of biomimetic coenzymes

application of complexes of multi-enzyme

ivBT synthesis of sulfated glycans and AI-assisted optimization of reaction conditions of ivBT synthesis

etc.

关键词

Keywords

references

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