Sugar 1.0 to 4.0: From conventional sugar production to precision biomanufacturing of healthy sugars
- 1State Key Laboratory of Tropical Crop Breeding, Institute of Tropical Bioscience and Biotechnology, Sanya Research Institute, Chinese Academy of Tropical Agricultural Sciences, Sanya, Hainan, 572024, China
- 2State Key Laboratory of Tropical Crop Breeding, Sanya Institute of Breeding and Multiplication, Hainan University, Sanya, 572025, China
Abstract
Excessive intake of free sugars is a major modifiable risk factor for obesity, type 2 diabetes and cardiovascular disease, and it is a global public-health priority to reduce dietary sugar while preserving sensory quality. Referred to here as "healthy sugars", the low-calorie monosaccharides D-allulose and D-tagatose combine sucrose-like sensory and bulking behavior with a distinct metabolic fate in humans and, for D-tagatose, with defence-inducing activity in plants. This review traces the evolution of sugar supply through four stages, from agricultural extraction of sucrose (Sugar 1.0) and enzymatic hydrolysis to high-fructose syrup (Sugar 2.0) to chemically synthesized high-intensity sweeteners (Sugar 3.0) and precision biomanufacturing of healthy sugars (Sugar 4.0). We review the molecular basis of healthy-sugar action in mammalian metabolic homeostasis and in plant sweet immunity, then compare manufacturing platforms, equilibrium-limited enzymatic epimerization, immobilized-enzyme and continuous-reactor processes, thermodynamically driven cell-free cascades, and cell-free CO₂-to-hexose synthesis, through a consolidated cross-platform comparison of conversion, titer, yield, scalability and technology readiness. We then set out an amyloplast-targeted compartmentalised design for sugar-crop chassis, a distinct phosphorylated route for D-tagatose, and a climate-adaptive sugarcane, sugar beet, sorghum manufacturing crops. Finally we examine the conditions under which a plant-chassis route could offer cost or carbon advantages, comparing feedstock, energy, separation and carbon-balance considerations across platforms, and comparing the ingredient and biosafety requirements applying in the United States, the European Union and China. The plant-chassis route is presented throughout as a design proposal requiring crop-level validation, and the prerequisites for its projected advantages are stated explicitly.
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BibTeX
@article{zhang2026sugar,
title = {{Sugar 1.0 to 4.0: From conventional sugar production to precision biomanufacturing of healthy sugars}},
author = {Zihao Zhang and Junlin Li and Jiahao Zhang and Qibin Wu and Fei Chen and Youxiong Que},
journal = {Biodesign research},
year = {2026},
month = oct,
doi = {10.1016/j.bidere.2026.100125},
url = {https://europepmc.org/article/PMC/PMC13717879},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sugar 1.0 to 4.0: From conventional sugar production to precision biomanufacturing of healthy sugars
AU - Zihao Zhang
AU - Junlin Li
AU - Jiahao Zhang
AU - Qibin Wu
AU - Fei Chen
AU - Youxiong Que
PY - 2026
DA - 2026/10/01
JO - Biodesign research
DO - 10.1016/j.bidere.2026.100125
UR - https://europepmc.org/article/PMC/PMC13717879
AB - Excessive intake of free sugars is a major modifiable risk factor for obesity, type 2 diabetes and cardiovascular disease, and it is a global public-health priority to reduce dietary sugar while preserving sensory quality. Referred to here as "healthy sugars", the low-calorie monosaccharides D-allulose and D-tagatose combine sucrose-like sensory and bulking behavior with a distinct metabolic fate in humans and, for D-tagatose, with defence-inducing activity in plants. This review traces the evolution of sugar supply through four stages, from agricultural extraction of sucrose (Sugar 1.0) and enzymatic hydrolysis to high-fructose syrup (Sugar 2.0) to chemically synthesized high-intensity sweeteners (Sugar 3.0) and precision biomanufacturing of healthy sugars (Sugar 4.0). We review the molecular basis of healthy-sugar action in mammalian metabolic homeostasis and in plant sweet immunity, then compare manufacturing platforms, equilibrium-limited enzymatic epimerization, immobilized-enzyme and continuous-reactor processes, thermodynamically driven cell-free cascades, and cell-free CO₂-to-hexose synthesis, through a consolidated cross-platform comparison of conversion, titer, yield, scalability and technology readiness. We then set out an amyloplast-targeted compartmentalised design for sugar-crop chassis, a distinct phosphorylated route for D-tagatose, and a climate-adaptive sugarcane, sugar beet, sorghum manufacturing crops. Finally we examine the conditions under which a plant-chassis route could offer cost or carbon advantages, comparing feedstock, energy, separation and carbon-balance considerations across platforms, and comparing the ingredient and biosafety requirements applying in the United States, the European Union and China. The plant-chassis route is presented throughout as a design proposal requiring crop-level validation, and the prerequisites for its projected advantages are stated explicitly.
SN - 2693-1257
ER -