合成生物学和AI驱动的甜味蛋白智能制造

杨申燕; 霍润甜; 邹沁; 孙丽超; 霍毅欣

doi:10.12211/2096-8280.2026-021

您当前的位置：

首页 >

文章列表页 >

合成生物学和AI驱动的甜味蛋白智能制造

特约评述 | 更新时间：2026-07-23

- 合成生物学和AI驱动的甜味蛋白智能制造
- Synthetic biology and AI-driven intelligent manufacturing of sweet proteins
- 合成生物学 2026年页码：1-21
- 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：
  
  杨申燕（2000—），女，硕士研究生，研究方向为合成生物学与代谢工程。
  孙丽超（1988-），女，副研究员，硕士生导师，研究方向为合成生物学与代谢工程。
  霍毅欣（1980-），男，教授，博士生导师，研究方向为合成生物学与代谢工程。
- 基金信息：
  
  国家重点研发计划(2024YFC3407000);通用技术航天医学研究与转化重点实验室开放课题(AMRTOP25015);北京市科技计划项目(Z251100000125015)
- DOI：10.12211/2096-8280.2026-021
  中图分类号： Q816
- 收稿：2026-04-07，
  
  修回：2026-07-12，
  
  网络首发：2026-07-23，
- 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

DEBRAS C , DESCHASAUX-TANGUY M , CHAZELAS E , et al . Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Santé Cohort [J ] . Diabetes Care . 2023 ; 46 ( 9 ): 1681 - 1690 .

刘倩 , 彭梓昌 , 王雅梦 , 等 . 合成生物学驱动的甜味蛋白创新生产 [J ] . 化学进展 , 2025 , 37 ( 8 ): 1131 - 1141 .

LIU Q , PENG Z C , WANG Y M , et al . Innovative production of sweet proteins driven by synthetic biology [J ] . Progress in Chemistry , 2025 , 37 ( 8 ): 1131 - 1141 .

ABRAMSON J , ADLER J , DUNGER J , et al . Accurate structure prediction of biomolecular interactions with AlphaFold 3 [J ] . Nature , 2024 , 630 ( 8016 ): 493 - 500 .

ANISHCHENKO I , PELLOCK SJ , CHIDYAUSIKU TM , et al . De novo protein design by deep network hallucination [J ] . Nature , 2021 ; 600 ( 7889 ): 547 - 552 .

NOVIK TS , KOVESHNIKOVA EI , KOTLOBAY AA , et al . Sweet-tasting natural proteins brazzein and monellin: safe sugar substitutes for the food industry [J ] . Foods , 2023 , 12 ( 22 ): 4065 .

MORRIS J A , MARTENSON R , DEIBLER G , et al . Characterization of monellin, a protein that tastes sweet [J ] . The Journal of Biological Chemistry , 1973 , 248 ( 2 ): 534 - 539 .

BOHAK Z , LI S L . The structure of monellin and its relation to the sweetness of the protein [J ] . Biochimica et Biophysica Acta , 1976 , 427 ( 1 ): 153 - 170 .

SUEZ J , KOREM T , ZEEVI D , et al . Artificial sweeteners induce glucose intolerance by altering the gut microbiota . Nature . 2014 ; 514 ( 7521 ): 181 - 186 .

KANT R . Sweet proteins-potential replacement for artificial low calorie sweeteners [J ] . Nutrition Journal , 2005 , 4 : 5 .

POTTER S M , ZHAO D , ROBERTS A , et al . Safety evaluation of honey truffle sweet protein produced from Komagataella phaffii [J ] . Food and Chemical Toxicology , 2026 , 211 : 115987 .

THEERASILP S , KURIHARA Y . Complete purification and characterization of the taste-modifying protein, miraculin, from miracle fruit [J ] . Journal of Biological Chemistry , 1988 , 263 ( 23 ): 11536 - 11539 .

施天元 , 曹国强 . 基因工程表达甜味蛋白的研究进展 [J ] . 食品工业科技 , 2023 , 44 ( 2 ): 453 - 459 .

SHI T Y , CAO G Q . Research progress on the expression of sweet proteins by genetic engineering [J ] . Science and Technology of Food Industry , 2023 , 44 ( 2 ): 453 - 459 .

CHUNG J H , KONG J N , CHOI H E , et al . Antioxidant, anti-inflammatory, and anti-allergic activities of the sweet-tasting protein brazzein [J ] . Food Chemistry , 2018 , 267 : 163 - 169 .

DONNARUMMA F , LEONE S , DELFI M , et al . Probing structural changes during amyloid aggregation of the sweet protein MNEI [J ] . The FEBS Journal , 2020 , 287 ( 13 ): 2808 - 2822 .

LEE HM , PARK SW , LEE SJ , et al . Optimized production and quantification of the tryptophan-deficient sweet-tasting protein brazzein in Kluyveromyces lactis [J ] . Preparative Biochemistry and Biotechnology , 2019 , 49 ( 8 ): 790 - 799 .

NEIERS F , BELLOIR C , POIRIER N , et al . Comparison of Different Signal Peptides for the Efficient Secretion of the Sweet-Tasting Plant Protein Brazzein in Pichia pastoris [J ] . Life , 2021 , 11 ( 1 ): 46 .

高鹏 , 张胜梦 , 孙元伟 , 等 . 毕赤酵母高效合成甜味蛋白Brazzein [J ] . 食品科学 , 2025 , 46 ( 17 ): 111 - 119 .

GAO P , ZHANG S M , SUN Y W , et al . Efficient synthesis of sweet protein brazzein by Komagataella phaffii [J ] . Food Science , 2025 , 46 ( 17 ): 111 - 119 .

DANIELL S , MELLITS KH , FAUS I , et al . Refolding the sweet-tasting protein thaumatin II from insoluble inclusion bodies synthesised in Escherichia coli [J ] . Food Chemistry , 2000 , 71 ( 1 ): 105 - 110 .

MORALEJO FJ , CARDOZA RE , GUTIÉRREZ S , et al . Overexpression and lack of degradation of thaumatin in an aspergillopepsin A-defective mutant of Aspergillus awamori containing an insertion in the pepA gene [J ] . Applied Microbiology and Biotechnology , 2000 , 54 ( 6 ): 772 - 777 .

NICHOLAS CHUA B , GUO WM , TENG WONG H , et al . A sweeter future: using protein language models for exploring sweeter brazzein homologs [J ] . Food Chemistry , 2023 , 426 : 136580

JOSEPH JA , AKKERMANS S , VAN IMPE JFM . Effects of Temperature and pH on Recombinant Thaumatin II Production by Pichia pastoris [J ] . Foods , 2022 , 11 ( 10 ): 1438 .

XIAOLI ZHANG , TAKESHI ITO , KEIJI KONDO , et al . Production of single chain recombinant monellin by high cell density culture of genetically engineered Candida utilis using limited feeding of sodium ions [J ] . Journal of Chemical Engineering of Japan , 2002 , 35 ( 7 ): 654 - 659 .

JIA L , TU T , HUAI Q , et al . Enhancing monellin production by Pichia pastoris at low cell induction concentration via effectively regulating methanol metabolism patterns and energy utilization efficiency [J ] . PLoS One , 2017 , 12 ( 10 ): e0184602 .

Chen Z , Li Z , Yu N , et al . Expression and secretion of a single-chain sweet protein, monellin, in Saccharomyces cerevisiae by an α-factor signal peptide [J ] . Biotechnology Letters , 2011 , 33 ( 4 ): 721 - 725 .

LIU J , YAN DZ , ZHAO SJ . Expression of monellin in a food-grade delivery system in Saccharomyces cerevisiae [J ] . Journal of the Science of Food and Agriculture , 2015 , 95 ( 13 ): 2646 - 2651 .

CHEN Z , HENG C , LI Z , et al . Expression and secretion of a single-chain sweet protein monellin in Bacillus subtilis by sacB promoter and signal peptide [J ] . Applied Microbiology and Biotechnology , 2007 , 73 ( 6 ): 1377 - 1381 .

JIA L , LI T , YANG Z , et al . Enhancing monellin production in Pichia pastoris fed-batch fermentation through an efficient on-line methanol/sorbitol co-feeding strate gy [J ] . Journal of Cleaner Production , 2022 , 369 : 133350 .

TOMOMI MATSUYAMA , MAKIKO SATOH , RIEKO NAKATA , et al . Functional Expression of Miraculin, a Taste-Modifying Protein in Escherichia Coli [J ] . The Journal of Biochemistry , 2009 , 145 ( 4 ): 445 – 450 .

BERLEC A , TOMPA G , SLAPAR N , et al . Optimization of fermentation conditions for the expression of sweet-tasting protein brazzein in Lactococcus lactis [J ] . Letters in Appled Microbiology , 2008 , 46 ( 2 ): 227 - 231 .

POIRIER N , ROUDNITZKY N , BROCKHOFF A , et al . Efficient production and characterization of the sweet-tasting brazzein secreted by the yeast Pichia pastoris [J ] . Journal of Agricultural and Food Chemistry , 2012 , 60 ( 39 ): 9807 - 9814 .

YAN S , SONG H , PANG DX , et al . Expression of plant sweet protein brazzein in the milk of transgenic mice [J ] . PLoS One , 2013 , 8 ( 10 ): e76769 .

FIRSOV A , SHALOIKO L , KOZLOV O , et al . Purification and characterization of recombinant supersweet protein thaumatin II from tomato fruit [J ] . Protein Expression and Purification , 2016 , 123 : 1 - 5 .

LAMPHEAR BJ , BARKER DK , BROOKS CA , et al . Expression of the sweet protein brazzein in maize for production of a new commercial sweetener [J ] . Plant Biotechnology Journal , 2005 , 3 ( 1 ): 103 - 114 .

LOZANO TEROL G , GALLEGO-JARA J , SOLA MARTÍNEZ RA , et al . Impact of the expression system on recombinant protein production in Escherichia coli BL21 [J ] . Frontiers in Microbiology , 2021 , 12 : 682001 .

JIANG RZ , YUAN ST , ZHOU YL , et al . Strategies to overcome the challenges of low or no expression of heterologous proteins in Escherichia coli [J ] . Biotechnol Advances , 2024 , 75 : 108417 .

HUNG CY , CHENG LH , YEH CM . Functional expression of recombinant sweet-tasting protein brazzein by Escherichia coli and Bacillus licheniformis [J ] . Food Biotechnology , 2019 , 33 ( 3 ): 251 - 271 .

MACAULEY-PATRICK S , FAZENDA M L , MCNEIL B , et al . Heterologous protein production using the Pichia pastoris expression system [J ] . Yeast , 2005 , 22 ( 4 ): 249 - 270 .

TANG N , LIU JC , CHENG YQ . Potential improvement of the thermal stability of sweet-tasting proteins by structural calculations [J ] . Food Chemistry , 2021 , 345 : 128750 .

刘毅 , 卢尚阳 , 王语晴 , 等 . 甜味蛋白monellin高甜度、强热稳定性突变体的分子构建及性质研究 [J ] . 中国食品学报 , 2024 , 24 ( 8 ): 53 - 61

LIU Y , LU S Y , WANG Y Q , et al . Molecular construction and characterization of high-sweetness and thermostable mutants of the sweet protein monellin [J ] . Journal of Chinese Institute of Food Science and Technology , 2024 , 24 ( 8 ): 53 - 61 .

YANG L , ZHU K K , YU H F , et al . The flexible loop is a new sweetness determinant site of the sweet - tasting protein: Characterization of novel sweeter mutants of the single -chain monellin (MNEI) [J ] . Chemical Senses , 2019 , 44 ( 8 ): 607 - 614 .

LEONE S , PICA A , MERLINO A , et al . Sweeter and stronger: Enhancing sweetness and stability of the single chain monellin MNEI through molecular design [J ] . Scientific Reports , 2016 , 6 ( 1 ): 34045

HELLEKANT G , DANILOVA V . Brazzein a small, sweet protein: discovery and physiological overview [J ] . Chemical Senses , 2005 , 30 ( Suppl 1 ): i88 - i89 .

LUCIGNANO R , SPADACCINI R , MERLINO A , et al . Structural insights and aggregation propensity of a super-stable monellin mutant: a new potential building block for protein-based nanostructured materials [J ] . International Journal of Biological Macromolecules , 2024 , 254 ( Pt 1 ): 127775 .

ASSADI-PORTER FM , ACETI DJ , CHENG H , et al . Efficient production of recombinant brazzein, a small, heat-stable, sweet-tasting protein of plant origin [J ] . Archives of Biochemistry and Biophysics , 2000 , 376 ( 2 ): 252 - 258 .

MASUDA T , SUZUKI M , YAMASAKI M , et al . Subatomic structure of orthorhombic thaumatin at 0.89 Å reveals that highly flexible conformations are crucial for thaumatin sweetness [J ] . Biochemical and Biophysical Research Communications , 2024 , 703 : 149601 .

MING D , HELLEKANT G . Brazzein, a new high-potency thermostable sweet protein from Pentadiplandra brazzeana B [J ] . FEBS Letters , 1994 , 355 ( 1 ): 106 - 108 .

FARAG MA , REZK MM , HAMDI ELASHAL M , et al . An updated multifaceted overview of sweet proteins and dipeptides as sugar substitutes; the chemistry, health benefits, gut interactions, and safety [J ] . Food Research International , 2022 , 162 ( Pt A ): 111853 .

LIU X , MAEDA S , HU Z , et al . Purification, complete amino acid sequence and structural characterization of the heat-stable sweet protein, Mabinlin II [J ] . European Journal of Biochemistry , 1993 , 211 ( 1/2 ): 281 - 287 .

卢尚阳 , 常诗瑜 , 王语晴 , 等 . 甜味蛋白质基因工程与分子改性研究进展 [J ] . 生物工程学报 , 2025 , 41 ( 02 ): 559 - 573 ..

LU S Y , CHANG S Y , WANG Y Q , et al . Research progress in genetic engineering and molecular modification of sweet proteins [J ] . Chinese Journal of Biotechnology , 2025 , 41 ( 2 ): 559 - 573 .

杨阳 , 李淑燕 , 倪元颖 . 甜味蛋白Thaumatin研究进展及在食品工业中的应用 [J ] . 中国食品添加剂 , 2012 , ( 05 ): 171 - 176 .

YANG Y , LI S Y , NI Y Y . Research progress of the sweet protein thaumatin and its application in the food industry [J ] . China Food Additives , 2012 , ( 5 ): 171 - 176 .

张泽生 , 李雨蒙 , 孙明哲 , 等 . 天然甜味蛋白索马甜的研究进展 [J ] . 中国食品添加剂 , 2018 ( 5 ): 186 - 189 .

ZHANG Z S , LI Y M , SUN M Z , et al . Research progress of the natural sweet protein thaumatin [J ] . China Food Additives , 2018 , ( 5 ): 186 - 189 .

BAYRAM H M , OZTURKCAN A . Added sugars and non-nutritive sweeteners in the food supply: Are they a threat for consumers? [J ] . Clinical Nutrition ESPEN , 2022 , 49 : 442 - 448 .

CASTRO-MUÑOZ R , CORREA-DELGADO M , CÓRDOVA-ALMEIDA R , et al . Natural sweeteners; Sources, extraction and current uses in foods and food industrie [J ] . Food Chemistry , 2022 , 370 : 130991 .

谭家忠 , 廖娜 , 张宝堂 , 等 . 天然甜味剂的开发应用及展望 [J ] . 中国食品添加剂 , 2022 , 33 ( 1 ): 32 - 39 .

TAN J Z , LIAO N , ZHANG B T , et al . Development, application and prospects of natural sweeteners [J ] . China Food Additives , 2022 , 33 ( 1 ): 32 - 39 .

谢新春 , 王红波 , 胡思前 , 等 . 一种基于微生物发酵从非洲竹芋中提取索马甜的方法 : CN111574607B [P ] . 2023 .

XIE X C , WANG H B , HU S Q , et al . A method for extracting thaumatin from Thaumatococcus daniellii based on microbial fermentation : CN111574607B [P ] . 2023 .

朱淩宣 , 崔鑫 , 胡善桐 , 等 . 毕赤酵母全蛋白质组信号肽及分泌蛋白分析 [J ] . 生物工程学报 , 2024 , 40 ( 03 ): 834 - 846 .

ZHU L X , CUI X , HU S T , et al . Proteome-wide analysis of signal peptides and secreted proteins in Pichia pastoris [J ] . Chinese Journal of Biotechnology , 2024 , 40 ( 3 ): 834 - 846 .

PARSEKAR N , AKKERMANS S , KOZAK D , et al . Enhancing recombinant thaumatin production by Komagataella phaffii through cold atmospheric helium plasma jet [J ] . Scientific Reports ,, 2025 , 15 : 39397 .

国家市场监督管理总局 , 国家卫生健康委员会 . 食品安全国家标准食品添加剂索马甜 : GB 1886.321—2021 [S ] . 北京 : 中国标准出版社 , 2021 .

State Administration for Market Regulation ; National Health Commission of the People's Republic of China . National food safety standard—Food additive thaumatin : GB 1886.321-2021 [S ] . Beijing : China Standards Press , 2021 .

张连忠 , 孙涛 , 高帅 . 甜味蛋白Brazzein的研究进展 [J ] . 唐山师范学院学报 , 2007 , ( 05 ): 29 - 32 .

ZHANG L Z , SUN T , GAO S . Research progress on the sweet protein brazzein [J ] . Journal of Tangshan Normal University , 2007 , ( 5 ): 29 - 32 .

NAGATA K , HONGO N , KAMEDA Y . The structure of brazzein, a sweet-tasting protein from the wild African plant Pentadiplandra brazzeana [J ] . Acta Crystallographica Section D Biological Crystallography , 2013 , 69 : 642 - 647 .

ASSADI-PORTER F M , ACETI D J , MARKLEY J L . Sweetness determinant sites of brazzein, a small, heat-stable, sweet-tasting protein [J ] . Archives of Biochemistry and Biophysics , 2000 , 376 ( 2 ): 259 - 265 .

SHI Z , XU W , WU L , et al . Structural and functional characterization of human sweet taste receptor [J ] . Nature , 2025 , 645 : 801 - 808 .

史勇 , 张明军 , 张英 , 等 . 甜味蛋白Brazzein基因酵母表达系统的建立 [J ] . 吉林农业大学学报 , 2010 , 32 ( 01 ): 43 - 46 .

SHI Y , ZHANG M J , ZHANG Y , et al . Construction of a yeast expression system for the sweet protein brazzein gene [J ] . Journal of Jilin Agricultural University , 2010 , 32 ( 1 ): 43 - 46 .

KIM S H , KANG C H , KIM R , et al . Redesigning a sweet protein: Increased stability and renaturability [J ] . Protein Engineering , 1989 , 2 ( 8 ): 571 - 575 .

QI T , LI X , LAI L , et al . Boiling-Resistant Single-Chain Sweet Protein Monellin as a Safe and Effective Sugar Alternative for Metabolic and Glycemic Management in Mice [J ] . Foods , 2025 , 14 ( 21 ): 3667 .

邹嘉讯 , 张语桐 , 杨洋 , 等 . 马槟榔甜味蛋白在大肠杆菌BL21中的异源表达及摇瓶发酵条件优化 [J ] . 化学与生物工程 , 2025 , 42 ( 12 ): 53 - 59 .

ZOU J X , ZHANG Y T , YANG Y , et al . Heterologous expression of mabinlin sweet protein in Escherichia coli BL21 and optimization of shake-flask fermentation conditions [J ] . Chemistry & Bioengineering , 2025 , 42 ( 12 ): 53 - 59 .

NAKAJIMA K , ASAKURA T , MARUYAMA J , et al . Extracellular production of neoculin, a sweet-tasting heterodimeric protein with taste-modifying activity, by Aspergillus oryzae [J ] . Applied and Environmental Microbiology , 2006 , 72 ( 5 ): 3716 - 3723 .

TONG M , DUAN S , WANG L , et al . Molecular mechanism of aspartame recognition by the human sweet taste receptor T1R2-T1R3 revealed by homology modeling and molecular dynamics simulations [J ] . Journal of Computer-Aided Molecular Design , 2026 , 40 ( 1 ): 74 .

JUEN Z , LU Z , YU R , et al . The structure of human sweetness [J ] . Cell , 2025 , 188 ( 15 ): 4141 - 4153 .

LAFFITTE A , NEIERS F , BRIAND L . Functional roles of the sweet taste receptor in oral and extraoral tissues [J ] . Current Opinion in Clinical Nutrition and Metabolic Care , 2014 , 17 ( 4 ): 379 - 385 .

VO P , CONNORS DE , SHARKEY BP , et al . Sweet protein allosteric binding and activation of the human T1R2/R3 sweet receptor: A simulation model validated by in vitro receptor activation assay [J ] . Biochemistry , 2026 , 65 : 399 - 416 .

何明娟 , 刘宁 , 邹曙明 , 等 . 马槟榔甜蛋白基因(MabinlinⅡ)的密码子优化及其在大肠杆菌中的表达 [J ] . 食品工业科技 , 2019 , 40 ( 18 ): 78 - 84 .

HE M J , LIU N , ZOU S M , et al . Codon optimization of the sweet protein gene Mabinlin II and its expression in Escherichia coli [J ] . Science and Technology of Food Industry , 2019 , 40 ( 18 ): 78 - 84 .

何明娟 , 邹曙明 , 蒋霞云 , 等 . 甜味蛋白特性及其表达的研究进展 [J ] . 生物化工 , 2018 , 4 ( 5 ): 105 - 108 .

HE M J , ZOU S M , JIANG X Y , et al . Research progress on the properties and expression of sweet proteins [J ] . Biological Chemical Engineering , 2018 , 4 ( 5 ): 105 - 108 .

MORINI G , BASSOLI A , TEMUSSI PA . From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2-T1R3 receptor [J ] . Journal of Medicinal Chemistry , 2005 , 48 ( 17 ): 5520 - 5529 .

TEMUSSI PA . Natural sweet macromolecules: how sweet proteins work [J ] . Cellular and Molecular Life Sciences , 2006 , 63 ( 16 ): 1876 - 1888 .

SHIMIZU-IBUKA A , MORITA Y , TERADA T , et al . Crystal structure of neoculin: insights into its sweetness and taste-modifying activity [J ] . Journal of Molecular Biology , 2006 , 359 ( 1 ): 148 - 158 .

TANCREDI T , PASTORE A , SALVADORI S , et al . Interaction of sweet proteins with their receptor. A conformational study of peptides corresponding to loops of brazzein, monellin and thaumatin [J ] . European Journal of Biochemistry , 2004 , 271 ( 11 ): 2231 - 2240 .

SHIMIZU-IBUKA A , NAKAI Y , NAKAMORI K , et al . Biochemical and genomic analysis of neoculin compared to monocot mannose-binding lectins [J ] . Journal of Agricultural and Food Chemistry , 2008 , 56 ( 13 ): 5338 .

KASHANI-AMIN E , FARAJI H , NOURIYENGEJEH S , et al . Structure-sweetness relationship of sweet proteins: a systematic review on "sweet protein" studies as a sub-group of "sweetener" investigations [J ] . Moscow Univ Biol Sci Bull , 2021 , 76 ( 4 ): 175 - 190 .

HAO S , GUTHRIE B , KIM KS , et al . Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments [J ] . Communications Chemistry , 2024 , 7 ( 1 ): 236 .

白淑锦 , 胡康琦 , 黄守法 , 等 . 索马甜在毕赤酵母中的高效表达 [J/OL ] . 食品与发酵工业 , 1 - 16 .

BAI S J , HU K Q , HUANG S F , et al . Efficient expression of thaumatin in Pichia pastoris [J/OL ] . Food and Fermentation Industries , 1 - 16 .

SATOSHI OKUBO , TOMIKO ASAKURA , KAZUE OKUBO , et al . Neoculin, a taste-modifying sweet protein, accumulates in ripening fruits of cultivated Curculigo latifolia [J ] . Journal of Plant Physiology , 2008 , 165 ( 18 ): 1964 - 1969 .

DAMASCENO L M , HUANG C J , BAIRD E E . Co-overexpression of chaperones for enhanced secretion of heterologous proteins in Pichia pastoris [J ] . Applied Microbiology and Biotechnology , 2007 , 74 ( 2 ): 381 - 389 .

GASSER B , SALOHEIMO M , RINAS U , et al . Protein folding and conformational stress in microbial cells producing recombinant proteins: a host comparative overview [J ] . Microbial Cell Factories , 2008 , 7 : 11 .

KARBALAEI M , REZAEE SA , FARSIANI H . Pichia pastoris : A highly successful expression system for optimal synthesis of heterologous proteins [J ] . Journal of Cellular Physiology , 2020 , 235 ( 9 ): 5867 - 5881 .

DELFI M , EMENDATO A , LEONE S , et al . A Super Stable Mutant of the Plant Protein Monellin Endowed with Enhanced Sweetness [J ] . Life (Basel) , 2021 , 11 ( 3 ): 236 .

LIU Y , XU J , MA M , et al . Computational design towards a boiling-resistant single-chain sweet protein monellin [J ] . Food Chemistry , 2024 , 440 : 138279 .

YOU T , SHI S , CHEN Cet al . Structural Basis for the Exceptional Thermal Stability of the Boiling-Resistant Sweet Protein MNEI [J ] . Journal of Agricultural and Food Chemistry , 2025 , 73 ( 25 ): 15959 - 15966 .

BILAL M , JI L , XU S , et al . Bioprospecting and biotechnological insights into sweet-tasting proteins by microbial hosts: a review [J ] . Bioengineered , 2022 , 13 ( 4 ): 9815 - 9828 .

MASUDA T , KITABATAKE N . Developments in biotechnological production of sweet proteins [J ] . Journal of Bioscience and Bioengineering , 2006 , 102 ( 5 ): 375 - 89 .

TEMUSSI PA . Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2-T1R3 receptor [J ] . FEBS Letters , 2002 , 526 ( 1-3 ): 1 - 4 .

SPADACCINI R , TRABUCCO F , SAVIANO G , et al . The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI [J ] . Journal of Molecular Biology , 2003 , 328 ( 3 ): 683 - 92 .

MADANI A , KRAUSE B , GREENE E R , et al . Large language models generate functional protein sequences across diverse families [J ] . Nature Biotechnology , 2023 , 41 ( 8 ): 1099 - 1106 .

MA M , SHI S , HUANG Z , et al . Enhancing the stability of sweet protein neoculin for food applications using computational strategies [J ] . Journal of Agricultural and Food Chemistry , 2025 , 73 ( 11 ): 6867 - 6877 .

REN Z , JIANG L , DI Y , et al . CodonBERT: a BERT-based architecture tailored for codon optimization using the cross-attention mechanism [J ] . Bioinformatics , 2024 , 40 ( 7 ): btae330 .

ZHAO X , WANG C , ZHENG Y , et al . New Insight Into the Structure-Activity Relationship of Sweet-Tasting Proteins: Protein Sector and Its Role for Sweet Properties [J ] . Frontiers in Nutrition , 2021 , 8 : 691368 .

JUMPER J , EVANS R , PRITZEL A , et al . Highly accurate protein structure prediction with AlphaFold [J ] . Nature , 2021 , 596 ( 7873 ): 583 - 589 .

WATSON JL , JUERGENS D , BENNETT NR , et al . De novo design of protein structure and function with RFdiffusion [J ] . Nature , 2023 , 620 ( 7976 ): 1089 - 1100 .

LIN Z , AKIN H , RAO R , et al . Evolutionary-scale prediction of atomic-level protein structure with a language model [J ] . Science , 2023 , 379 ( 6637 ): 1123 - 1130

BAEK M , DIMAIO F , ANISHCHENKO I , et al . Accurate prediction of protein structures and interactions using a three-track neural network [J ] . Science , 2021 , 373 ( 6557 ): 871 - 876 .

FALLAHPOUR A , GUREGHIAN V , FILION GJ , et al . CodonTransformer: a multispecies codon optimizer using context-aware neural networks [J ] . Nature Communications , 2025 , 16 ( 1 ): 3205 .

DING S , ZHANG Y . De novo design of protein binders targeting the human sweet taste receptor as potential sweet proteins [EB/OL ] . arXiv . 20 26: 2601 . 14574 .

RADIVOJEVIĆ T , COSTELLO Z , WORKMAN K , et al . A machine learning Automated Recommendation Tool for synthetic biology [J ] . Nature Communications , 2020 , 11 : 4879 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

蛋白质工程在医药产业中的应用

人工智能蛋白质结构设计算法研究进展

人工智能辅助的蛋白质工程

基于微生物电合成的一碳生物转化

基于生物体-材料杂化体系的低碳生物合成的研究进展