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New technologies and industrialization progress in healthy sugar biomanufacturing based on in vitro synthetic biology
Invited Review | 更新时间：2026-09-04
|
New technologies and industrialization progress in healthy sugar biomanufacturing based on
in vitro synthetic biology- 基于体外合成生物学的健康糖生物制造新技术与产业化进展
- Synthetic Biology Journal Vol. 7, Issue 4, Pages: 763-780(2026)
- 作者机构：
1.中国科学院天津工业生物技术研究所，低碳合成工程生物学全国重点实验室，天津 300308
2.中国科学院天津工业生物技术研究所，体外合成生物学中心，天津 300308
- 作者简介：
- 基金信息：
DOI：10.12211/2096-8280.2025-054
CLC： Q81Received：04 June 2025，
Revised：2025-08-05，
Published：31 August 2026
- 稿件说明：
移动端阅览
石婷， 陈雪梅， 张以恒. 基于体外合成生物学的健康糖生物制造新技术与产业化进展［J］. 合成生物学， 2026， 7（4）： 763-780
SHI Ting， CHEN Xuemei， ZHANG Yi-Heng P. Job. New technologies and industrialization progress in healthy sugar biomanufacturing based on in vitro synthetic biology［J］. Synthetic Biology Journal， 2026， 7（4）： 763-780
石婷， 陈雪梅， 张以恒. 基于体外合成生物学的健康糖生物制造新技术与产业化进展［J］. 合成生物学， 2026， 7（4）： 763-780 DOI： 10.12211/2096-8280.2025-054.
SHI Ting， CHEN Xuemei， ZHANG Yi-Heng P. Job. New technologies and industrialization progress in healthy sugar biomanufacturing based on in vitro synthetic biology［J］. Synthetic Biology Journal， 2026， 7（4）： 763-780 DOI： 10.12211/2096-8280.2025-054.
New technologies and industrialization progress in healthy sugar biomanufacturing based on in vitro synthetic biology
摘要
随着全球健康意识的提升，消费者对低热量、功能性的天然糖（简称健康糖）需求增长。酶催化与体外生物转化（
in vitro
BioTransformation，ivBT）是健康糖的工业生物制造的两大平台技术。酶法生产果葡糖浆的商业化成功开启淀粉糖产业，随后Izumoring策略推动酶法生产稀有糖，但受原料依赖、转化率低、分离成本高、辅酶循环利用等因素使该策略难以大规模生产健康糖（如D-塔格糖、L-阿拉伯糖）。基于ivBT平台，我们开发了首个非天然戊单糖4-差向异构酶，实现D型与L型戊糖的直接转换，无需经过糖醇中间体，打通D-木糖向L-阿拉伯糖转化新路径；淀粉制肌醇已成功实现产业化，验证了Zhang策略（“无ATP磷酸化-异构-脱磷酸”策略）的生物制造优势，该策略拓展至廉价多糖原料合成D-塔格糖、D-阿洛酮糖、D-甘露糖等健康糖；“二氧化碳合成糖类”技术突破了植物光合作用的能效低与速度慢的瓶颈，为以第三代原料合成健康糖及其衍生物开辟新途径。ivBT平台取得了系列突破性进展，有望为开发“低成本、高可及性、高功能性”的健康糖提供核心支撑，引领甜味剂产业的新变革。
Abstract
With the deepening global focus on health
there is a surging demand for natural sugars that are low in calories
offer delightful sweetness
and provide beneficial health functions. However
the traditional sugar industry faces significant constraints related to health concerns
cost
and scalability. Enzymatic biocatalysis and
in vitro
BioTransformation (ivBT) are two pivotal technological platforms in biomanufacturing
playing an increasingly vital role in biomanufacturing of healthy sugars. The successful commercialization of high-fructose corn syrup opened the door of the starchy sweetener industry. Later
the Izumoring strategy opened the door to the rare sugars industry that is based on by enzymatic isomerization and oxidization-reduction of sugars. However
the key products made by the Izumoring strategy suffer from high reliance on limited feedstocks
low product yields due to equilibria of i
somerization
high separation costs
and/or the use of costly NAD(P) for the oxidization-reduction of sugars. Based on the ivBT platform
we have developed the first new-to-nature pentose 4-epimerase
enabling the direct conversion of D-type to L-type pentoses without sugar alcohol intermediates
thereby establishing an innovative route for the biotransformation of D-xylose to L-arabinose. The successful industrial-scale production of
myo
-inositol from starch has validated the biomanufacturing advantages of Zhang strategy (“ATP-free Phosphorylation-Isomerization-Dephosphorylation” strategy) as applied to ivBT. This approach has since been extended to the synthesis of a few healthy sugars
such as D-tagatose
D-allulose
and D-mannose
from abundant polysaccharides including starch
cellulose
and sucrose
showing great potential for industrial application. Furthermore
the “carbon dioxide to sugar” ivBT platform overcomes the low energy efficiency and slow productivity bottlenecks of natural plant photosynthesis
opening up a new door for the synthesis of healthy sugars from the third-generation feedstock of CO
2
. This ivBT platform has achieved multiple breakthroughs
such as the reconstruction of artificial enzymatic pathways for the biosynthesis of healthy sugars
low-cost biomanufacturing of multi-enzyme molecular machines equipped with thermostable enzyme bricks
great compatibility of multi-enzyme co-immobilization for prolonging enzyme life-time
promotion of the PE value (Product-to-Enzyme Weight Ratio) of multi-enzyme molecular machines
and low-cost separation and purification of healthy sugars. As a disruptive innovation in biomanufacturing
ivBT motivates the rapid development in the biomanufacturing of “affordable
accessible
and effective” healthy sugars and holds promise to drive a new wave of transformation in the sweetener industry.
2
关键词
Keywords
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SHI Ting
CHEN Xuemei
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Key Laboratory of Engineering Biology for Low-Carbon Manufacturing，Tianjin Institute of Industrial Biotechnology，Chinese Academy of Sciences
In vitro Synthetic Biology Center，Tianjin Institute of Industrial Biotechnology，Chinese Academy of Sciences
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