Core elements and key technologies of ivBT-based glycan synthesis

PEI Caixia; LI Jianjun; DU Yuguang

doi:10.12211/2096-8280.2025-064

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Core elements and key technologies of ivBT-based glycan synthesis

Invited Review | 更新时间：2026-09-04

- Core elements and key technologies of ivBT-based glycan synthesis
- 糖质ivBT生物合成的核心元件及关键技术
- Synthetic Biology Journal Vol. 7, Issue 4, Pages: 798-817(2026)
- 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：
- 基金信息：
- DOI：10.12211/2096-8280.2025-064
  CLC： Q814.9
- Received：23 June 2025，
  
  Revised：2025-08-10，
  
  Published：31 August 2026
- 稿件说明：
移动端阅览
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， 2026， 7（4）： 798-817

PEI Caixia， LI Jianjun， DU Yuguang. Core elements and key technologies of ivBT-based glycan synthesis［J］. Synthetic Biology Journal， 2026， 7（4）： 798-817
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， 2026， 7（4）： 798-817 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， 2026， 7（4）： 798-817 DOI： 10.12211/2096-8280.2025-064.

摘要

糖质（glycan）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他生物大分子。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 fundamental biomolecules of life

playing important roles in a vast array of biological processes. These include cell growth and proliferation

immune responses

angiogenesis

and tumor cell metastasis. They are also crucial in toxin interaction

protein folding and degradation

cell-cell communications

and cell-pathogen

interactions. Consequently

glycans are intimately linked to human health and disease

influencing the occurrence

development

and metastasis of tumor

as well as inflammation

viral or bacterial infections. 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 isolating and purifying glycans with defined structures from natural sources remains unfeasible

synthesis stands as the most reliable method for obtaining them.

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 re

action conditions of ivBT synthesis

etc

关键词

Keywords

references

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