Synthetic biology and AI-driven intelligent manufacturing of sweet proteins

YANG Shenyan; HUO Runtian; ZOU Qin; SUN Lichao; HUO Yixin

doi:10.12211/2096-8280.2026-021

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Synthetic biology and AI-driven intelligent manufacturing of sweet proteins

更新时间：2026-07-23

- Synthetic biology and AI-driven intelligent manufacturing of sweet proteins
- 合成生物学和AI驱动的甜味蛋白智能制造
- Synthetic Biology Journal Pages: 1-21(2026)
- 作者机构：
  
  1.北京理工大学生命学院 & 航天中心医院，北京 100081
  2.北京理工大学唐山研究院，河北唐山 063000
  3.牧原大厦未来食品中心牧原实验室，河南郑州 450016
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2026-021
  CLC： Q816
- Received：07 April 2026，
  
  Revised：2026-07-12，
  
  Online First：23 July 2026，
- 稿件说明：
移动端阅览
杨申燕，霍润甜，邹沁，孙丽超，霍毅欣. 合成生物学和AI驱动的甜味蛋白智能制造［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-021

YANG Shenyan， HUO Runtian， ZOU Qin， SUN Lichao， HUO Yixin. Synthetic biology and AI-driven intelligent manufacturing of sweet proteins［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-021
杨申燕，霍润甜，邹沁，孙丽超，霍毅欣. 合成生物学和AI驱动的甜味蛋白智能制造［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-021 DOI：

YANG Shenyan， HUO Runtian， ZOU Qin， SUN Lichao， HUO Yixin. Synthetic biology and AI-driven intelligent manufacturing of sweet proteins［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-021 DOI：

摘要

在全球“减糖”消费需求持续增长的背景下，甜味蛋白作为一类不直接参与血糖代谢的功能性蛋白，因其高甜度、优良感官特性及广阔应用前景而受到广泛关注。然而，其产业化应用仍面临生产成本高、蛋白稳定性不足以及甜味感官特征与蔗糖存在差异等挑战。本文系统梳理了索马甜、巴西甜蛋白、莫内林等八种典型甜味蛋白在结构特征、制备方法及甜味受体识别机制等方面的研究进展，综述了底盘细胞工程、表达元件优化及蛋白质工程改造等合成生物学策略在甜味蛋白生物制造中的应用与最新进展。进一步地，本文重点讨论了人工智能在新型甜味蛋白设计、表达量提升、稳定性优化、口感调控以及复杂食品体系适配等方向的创新应用与发展潜力，并探讨了甜味蛋白的技术经济性与产业化可行性，旨在为甜味蛋白的绿色生物制造、智能化设计及产业化开发提供参考。

Abstract

Under the growing global demand for sugar reduction

sweet proteins have emerged as promising natural sweeteners owing to their ultrahigh sweetness

favorable sensory attributes

and negligible impact on blood glucose metabolism. Despite their considerable commercial potential

large-scale application remains constrained by challenges including high production costs

limited protein stability

and sensory characteristics that differ from those of sucrose. This review systematically summarizes the current research progress on eight representative sweet proteins

including thaumatin

brazzein

monellin

mabinlin

neoculin

curculin

miraculin

and pentadin. Their sources

structural features

sweetness characteristics

and physicochemical properties are comprehensively discussed. Particular emphasis is placed on the molecular mechanisms underlying sweet taste perception

including the interaction of sweet proteins with the human sweet taste receptor and recent advances in elucidating receptor activation pathways through structural biology and computational modeling. These findings provide an important theoretical foundation for the rational design and optimization of sweet proteins. Furthermore

recent advances in synthetic biology-enabled biomanufacturing of sweet proteins are reviewed

covering chassis cell engineering

promoter and codon optimization

secretion pathway regulation

fermentation process development

and downstream purification strategies. The applications of protein engineering approaches

including rational design

directed evolution

computational redesign

and structure-guided mutagenesis

are also discussed with respect to improving protein expression

sweetness potency

thermostability

pH tolerance

and overall industrial applicability. Particular attention is devoted to the emerging role of artificial intelligence (AI) in sweet protein research and development. Recent breakthroughs in protein structure prediction

generative protein design

machine learning-assisted sequence optimization

and AI-driven codon engineering have significantly accelerated the discovery and engineering of sweet proteins. AI-based frameworks integrated with structural biology

molecular simulation

and Design-Build-Test-Learn (DBTL) cycles are enabling the development of novel sweet proteins with enhanced functionality and manufacturability. Moreover

advances in de novo protein design offer unprecedented opportunities for creating artificial sweet proteins beyond the limitations of naturally occurring protein scaffolds. Finally

this review discusses the techno-economic feasibility

regulatory considerations

and commercialization prospects of sweet protein production. Future developments are expected to arise from the convergence of synthetic biology

protein engineering

structural biology

and artificial intelligence

driving the transition from natural sweet protein optimization toward the rational creation of next-generation sweet proteins. These advances will facilitate the establishment of sustainable

intelligent

and economically viable production platforms

supporting the broader adoption of sweet proteins as key ingredients in the future healthy food industry.

关键词

Keywords

references

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