The synthesis, degradation and biological function of trehalose- 6-phosphate

Abstract

Trehalose-6-phosphate (T6P), an intermediate in trehalose metabolic pathways, is ubiquitously present in nearly all cellular organisms except vertebrates. The most well-characterized metabolic route involves its synthesis by trehalose-6-phosphate synthase (TPS) and dephosphorylation to trehalose by trehalose-6-phosphate phosphatase (TPP) in the TPS/TPP pathway. Besides, alternative trehalose metabolic pathways aslo exist. In addition to being the precursor of trehalose synthesis, T6P functions as a signal molecule regulating various biological processes. In plants, T6P inhibits SnRK1 (Sucrose-nonfermenting 1 Related Kinase 1), while in fungi, T6P primarily inhibits hexokinase and regulates glycolysis. Notably, TPS and TPP themselves also have some regulatory functions. Genetic studies reveal that deletion of TPS or TPP usually causes developmental and virulence defects in fungi, bacteria and invertebrates. Given that TPS and TPP have important biological functions in pathogenic fungi but are absent in humans and vertebrates, they are ideal targets for fungicide development. This review summarizes trehalose metabolic pathways and the multifaceted roles of T6P in plants, fungi and invertebrates, providing a comprehensive overview of its biological functions. Additionally, it discusses some reported TPS/TPP inhibitor to offer insights for pathogen control strategies.

Keywords

Trehalose- 6-phosphate / Metabolism pathway / Regulatory function / Virulence / Development / Biological Sciences / Biochemistry and Cell Biology

References

[1] AnderssonU, LevanderF, RådströmP. Trehalose-6-phosphate phosphorylase is part of a novel metabolic pathway for trehalose utilization in Lactococcus lactis. J Biol Chem, 2001, 276: 42707-42713.

[2] ArgüellesJC. Heat-shock response in a yeast tps1 mutant deficient in trehalose synthesis. FEBS Lett, 1994, 350: 266-270.

[3] AvidanO, MartinsMCM, FeilR, LohseM, GiorgiFM, SchlerethA, LunnJE, StittM. Direct and indirect responses of the Arabidopsis transcriptome to an induced increase in trehalose 6-phosphate. Plant Physiol, 2024.

[4] AvonceN, Mendoza-VargasA, MorettE, IturriagaG. Insights on the evolution of trehalose biosynthesis. BMC Evol Biol, 2006, 6: 109.

[5] Bell W, Sun W, Hohmann S, Wera S, Reinders A, de Virgilio C, Wiemken A, Thevelein JM (1998) Composition and functional analysis of the Saccharomyces cerevisiae trehalose synthase complex. J Biol Chem 273:33311–33319. https://doi.org/10.1074/jbc.273.50.33311.

[6] BlázquezMA, LagunasR, GancedoC, GancedoJM. Trehalose-6-phosphate, a new regulator of yeast glycolysis that inhibits hexokinases. FEBS Lett, 1993, 329: 51-54.

[7] BlázquezMA, SantosE, FloresCL, Martínez-ZapaterJM, SalinasJ, GancedoC. Isolation and molecular characterization of the Arabidopsis TPS1 gene, encoding trehalose-6-phosphate synthase. Plant J, 1998, 13: 685-689.

[8] BoniniBM, van DijckP, TheveleinJM. Uncoupling of the glucose growth defect and the deregulation of glycolysis in Saccharomyces cerevisiae Tps1 mutants expressing trehalose-6-phosphate-insensitive hexokinase from Schizosaccharomyces pombe. Biochim Biophys Acta, 2003, 1606: 83-93.

[9] BorgiaPT, MiaoY, DodgeCL. The orlA gene from Aspergillus nidulans encodes a trehalose-6-phosphate phosphatase necessary for normal growth and chitin synthesis at elevated temperatures. Mol Microbiol, 1996, 20: 1287-1296.

[10] ChenJ, ZhangD, YaoQ, ZhangJ, DongX, TianH, ChenJ, ZhangW. Feeding-based RNA interference of a trehalose phosphate synthase gene in the brown planthopper, Nilaparvata lugens. Insect Mol Biol, 2010, 19: 777-786.

[11] ChenJX, LyuZH, WangCY, ChengJ, LinT. RNA interference of a trehalose-6-phosphate synthase gene reveals its roles in the biosynthesis of chitin and lipids in Heortia vitessoides (Lepidoptera: Crambidae). Insect Sci, 2020, 27: 212-223.

[12] ChenQW, JinS, ZhangL, ShenQD, WeiP, WeiZM, WangSG, TangB. Regulatory functions of trehalose-6-phosphate synthase in the chitin biosynthesis pathway in Tribolium castaneum (Coleoptera: Tenebrionidae) revealed by RNA interference. Bull Entomol Res, 2018, 108: 388-399.

[13] ChenX, AbubakarYS, YangC, WangX, MiaoP, LinM, WenY, WuQ, ZhongH, FanY, ZhangM, WangZ, ZhouJ, ZhengW. Trehalose phosphate synthase complex-mediated regulation of trehalose 6-phosphate homeostasis is critical for development and pathogenesis in Magnaporthe oryzae. mSystems, 2021, 6: e0046221.

[14] ChenY, TangL, JiangZ, WangS, QiL, TianX, DengH, KongZ, GaoW, ZhangX, LiS, ChenM, ZhangX, DuanH, YangJ, PengYL, WangD, LiuJ. Dual-specificity inhibitor targets enzymes of the trehalose biosynthesis pathway. J Agric Food Chem, 2024, 72: 209-218.

[15] de VirgilioC, BürckertN, BellW, JenöP, BollerT, WiemkenA. Disruption of TPS2, the gene encoding the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex in Saccharomyces cerevisiae, causes accumulation of trehalose-6-phosphate and loss of trehalose-6-phosphate phosphatase activity. Eur J Biochem, 1993, 212: 315-323.

[16] Deroover S, Ghillebert R, Broeckx T, Winderickx J, Rolland F (2016) Trehalose-6-phosphate synthesis controls yeast gluconeogenesis downstream and independent of SNF1. FEMS Yeast Res 16:fow036. https://doi.org/10.1093/femsyr/fow036

[17] DoehlemannG, BerndtP, HahnM. Trehalose metabolism is important for heat stress tolerance and spore germination of Botrytis cinerea. Microbiology (Reading), 2006, 152: 2625-2634.

[18] EastmondPJ, van DijkenAJ, SpielmanM, KerrA, TissierAF, DickinsonHG, JonesJD, SmeekensSC, GrahamIA. Trehalose-6-phosphate synthase 1, which catalyses the first step in trehalose synthesis, is essential for Arabidopsis embryo maturation. Plant J, 2002, 29: 225-235.

[19] EisC, NidetzkyB. Characterization of trehalose phosphorylase from Schizophyllum commune. Biochem J, 1999, 341Pt 2385-393.

[20] EleutherioEC, AraujoPS, PanekAD. Role of the trehalose carrier in dehydration resistance of Saccharomyces cerevisiae. Biochim Biophys Acta, 1993, 1156: 263-266.

[21] EntzerothM, FlotowH, CondronP. Overview of high-throughput screening. Curr Protoc Pharmacol, 2009, 44: 9.4.1-9.4.27.

[22] FichtnerF, BarbierFF, FeilR, WatanabeM, AnnunziataMG, ChabikwaTG, HöfgenR, StittM, BeveridgeCA, LunnJE. Trehalose 6-phosphate is involved in triggering axillary bud outgrowth in garden pea (Pisum sativum L.). Plant J, 2017, 92: 611-623.

[23] FichtnerF, BarbierFF, AnnunziataMG, FeilR, OlasJJ, Mueller-RoeberB, StittM, BeveridgeCA, LunnJE. Regulation of shoot branching in Arabidopsis by trehalose 6-phosphate. New Phytol, 2021, 229: 2135-2151.

[24] FichtnerF, LunnJE. The role of trehalose 6-phosphate (Tre6P) in plant metabolism and development. Annu Rev Plant Biol, 2021, 72: 737-760.

[25] FigueroaCM, FeilR, IshiharaH, WatanabeM, KöllingK, KrauseU, HöhneM, EnckeB, PlaxtonWC, ZeemanSC, LiZ, SchulzeWX, HoefgenR, StittM, LunnJE. Trehalose 6-phosphate coordinates organic and amino acid metabolism with carbon availability. Plant J, 2016, 85: 410-423.

[26] FosterAJ, JenkinsonJM, TalbotNJ. Trehalose synthesis and metabolism are required at different stages of plant infection by Magnaporthe grisea. EMBO J, 2003, 22: 225-235.

[27] FrankA, MatiolliCC, VianaAJC, HearnTJ, KusakinaJ, BelbinFE, Wells NewmanD, YochikawaA, Cano-RamirezDL, ChembathA, Cragg-BarberK, HaydonMJ, HottaCT, VincentzM, WebbAAR, DoddAN. Circadian entrainment in Arabidopsis by the sugar-responsive transcription factor bZIP63. Curr Biol, 2018, 28: 2597-2606.e2596.

[28] FrisonM, ParrouJL, GuillaumotD, MasquelierD, FrançoisJ, ChaumontF, BatokoH. The Arabidopsis thaliana trehalase is a plasma membrane-bound enzyme with extracellular activity. FEBS Lett, 2007, 581: 4010-4016.

[29] GiaeverHM, StyrvoldOB, KaasenI, StrømAR. Biochemical and genetic characterization of osmoregulatory trehalose synthesis in Escherichia coli. J Bacteriol, 1988, 170: 2841-2849.

[30] GómezLD, BaudS, GildayA, LiY, GrahamIA. Delayed embryo development in the Arabidopsis trehalose-6-phosphate synthase 1 mutant is associated with altered cell wall structure, decreased cell division and starch accumulation. Plant J, 2006, 46: 69-84.

[31] GongC, YangZ, HuY, WuQ, WangS, GuoZ, ZhangY. Silencing of the BtTPS genes by transgenic plant-mediated RNAi to control Bemisia tabaci MED. Pest Manag Sci, 2022, 78: 1128-1137.

[32] HarthillJE, MeekSE, MorriceN, PeggieMW, BorchJ, WongBH, MackintoshC. Phosphorylation and 14–3-3 binding of Arabidopsis trehalose-phosphate synthase 5 in response to 2-deoxyglucose. Plant J, 2006, 47: 211-223.

[33] Hellens AM, Kreisz P, Humphreys JL, Feil R, Lunn JE, Dröge-Laser W, Beveridge CA, Fichtner F, Weiste C, Barbier FF (2023) The transcription factor bZIP11 acts antagonistically with trehalose 6-phosphate to inhibit shoot branching. bioRxiv. https://doi.org/10.1101/2023.05.23.542007

[34] HohmannS, BellW, NevesMJ, ValckxD, TheveleinJM. Evidence for trehalose-6-phosphate-dependent and -independent mechanisms in the control of sugar influx into yeast glycolysis. Mol Microbiol, 1996, 20: 981-991.

[35] HorlacherR, UhlandK, KleinW, EhrmannM, BoosW. Characterization of a cytoplasmic trehalase of Escherichia coli. J Bacteriol, 1996, 178: 6250-6257.

[36] HorlacherR, BoosW. Characterization of TreR, the major regulator of the Escherichia coli trehalose system. J Biol Chem, 1997, 272: 13026-13032.

[37] HottigerT, de VirgilioC, HallMN, BollerT, WiemkenA. The role of trehalose synthesis for the acquisition of thermotolerance in yeast. Ii. Physiological concentrations of trehalose increase the thermal stability of proteins in vitro. Eur J Biochem, 1994, 219: 187-193.

[38] HounsaCG, BrandtEV, TheveleinJ, HohmannS, PriorBA. Role of trehalose in survival of Saccharomyces cerevisiae under osmotic stress. Microbiology (Reading), 1998, 144Pt 3671-680.

[39] HubloherJJ, ZeidlerS, LamosaP, SantosH, AverhoffB, MüllerV. Trehalose-6-phosphate-mediated phenotypic change in Acinetobacter baumannii. Environ Microbiol, 2020, 22: 5156-5166.

[40] IshiharaH, AlseekhS, FeilR, PereraP, GeorgeGM, NiedźwieckiP, ArrivaultS, ZeemanSC, FernieAR, LunnJE, SmithAM, StittM. Rising rates of starch degradation during daytime and trehalose 6-phosphate optimize carbon availability. Plant Physiol, 2022, 189: 1976-2000.

[41] IshiharaR, TaketaniS, Sasai-TakedatsuM, KinoM, TokunagaR, KobayashiY. Molecular cloning, sequencing and expression of cDNA encoding human trehalase. Gene, 1997, 202: 69-74.

[42] KatoM, MiuraY, KettokuM, ShindoK, IwamatsuA, KobayashiK. Purification and characterization of new trehalose-producing enzymes isolated from the hyperthermophilic archae, Sulfolobus solfataricus KM1. Biosci Biotechnol Biochem, 1996, 60: 546-550.

[43] KernC, WolfC, BenderF, BergerM, NoackS, SchmalzS, IlgT. Trehalose-6-phosphate synthase from the cat flea Ctenocephalides felis and Drosophila melanogaster: gene identification, cloning, heterologous functional expression and identification of inhibitors by high throughput screening. Insect Mol Biol, 2012, 21: 456-471.

[44] KhanMA, Al Mamun KhanMA, MahfuzA, SanjanaJM, AhsanA, GuptaDR, HoqueMN, IslamT. Highly potent natural fungicides identified in silico against the cereal killer fungus Magnaporthe oryzae. Sci Rep, 2022, 12: 20232.

[45] KimB, LeeY, ChoiH, HuhWK. The trehalose-6-phosphate phosphatase Tps2 regulates ATG8 transcription and autophagy in Saccharomyces cerevisiae. Autophagy, 2021, 17: 1013-1027.

[46] KleinW, HorlacherR, BoosW. Molecular analysis of treB encoding the Escherichia coli enzyme II specific for trehalose. J Bacteriol, 1995, 177: 4043-4052.

[47] KolbeA, TiessenA, SchluepmannH, PaulM, UlrichS, GeigenbergerP. Trehalose 6-phosphate regulates starch synthesis via posttranslational redox activation of ADP-glucose pyrophosphorylase. Proc Natl Acad Sci U S A, 2005, 102: 11118-11123.

[48] KormishJD, McGheeJD. The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase. Dev Biol, 2005, 287: 35-47.

[49] KorteJ, AlberM, TrujilloCM, SysonK, Koliwer-BrandlH, DeenenR, KöhrerK, DeJesusMA, HartmanT, JacobsWRJr, BornemannS, IoergerTR, EhrtS, KalscheuerR. Trehalose-6-phosphate-mediated toxicity determines essentiality of otsB2 in Mycobacterium tuberculosis in vitro and in mice. PLoS Pathog, 2016, 12: e1006043.

[50] KushwahaS, SinghPK, ShahabM, PathakM, BhattacharyaSM. In vitro silencing of Brugia malayi trehalose-6-phosphate phosphatase impairs embryogenesis and in vivo development of infective larvae in jirds. PLoS Negl Trop Dis, 2012, 6: e1770.

[51] LewisJG, LearmonthRP, WatsonK. Induction of heat, freezing and salt tolerance by heat and salt shock in Saccharomyces cerevisiae. Microbiology (Reading), 1995, 141Pt 3687-694.

[52] LeymanB, van DijckP, TheveleinJM. An unexpected plethora of trehalose biosynthesis genes in Arabidopsis thaliana. Trends Plant Sci, 2001, 6: 510-513.

[53] LiZ, WeiX, TongX, ZhaoJ, LiuX, WangH, TangL, ShuY, LiG, WangY, YingJ, JiaoG, HuH, HuP, ZhangJ. The OsNAC23-Tre6P-SnRK1a feed-forward loop regulates sugar homeostasis and grain yield in rice. Mol Plant, 2022, 15: 706-722.

[54] LinQ, YangJ, WangQ, ZhuH, ChenZ, DaoY, WangK. Overexpression of the trehalose-6-phosphate phosphatase family gene AtTPPF improves the drought tolerance of Arabidopsis thaliana. BMC Plant Biol, 2019, 19: 381.

[55] LiuX, FuL, QinP, SunY, LiuJ, WangX. Overexpression of the wheat trehalose 6-phosphate synthase 11 gene enhances cold tolerance in Arabidopsis thaliana. Gene, 2019, 710: 210-217.

[56] LunnJE, FeilR, HendriksJH, GibonY, MorcuendeR, OsunaD, ScheibleWR, CarilloP, HajirezaeiMR, StittM. Sugar-induced increases in trehalose 6-phosphate are correlated with redox activation of ADPglucose pyrophosphorylase and higher rates of starch synthesis in Arabidopsis thaliana. Biochem J, 2006, 397: 139-148.

[57] LunnJE. Gene families and evolution of trehalose metabolism in plants. Funct Plant Biol, 2007, 34: 550-563.

[58] MartinsMC, HejaziM, FettkeJ, SteupM, FeilR, KrauseU, ArrivaultS, VoslohD, FigueroaCM, IvakovA, YadavUP, PiquesM, MetznerD, StittM, LunnJE. Feedback inhibition of starch degradation in Arabidopsis leaves mediated by trehalose 6-phosphate. Plant Physiol, 2013, 163: 1142-1163.

[59] MarutaK, HattoriK, NakadaT, KubotaM, SugimotoT, KurimotoM. Cloning and sequencing of trehalose biosynthesis genes from Arthrobacter sp. Q36. Biochim Biophys Acta, 1996, 1289: 10-13.

[60] MarutaK, HattoriK, NakadaT, KubotaM, SugimotoT, KurimotoM. Cloning and sequencing of trehalose biosynthesis genes from Rhizobium sp. M-11. Biosci Biotechnol Biochem, 1996, 60: 717-720.

[61] MeitzelT, RadchukR, McAdamEL, ThormählenI, FeilR, MunzE, HiloA, GeigenbergerP, RossJJ, LunnJE, BorisjukL. Trehalose 6-phosphate promotes seed filling by activating auxin biosynthesis. New Phytol, 2021, 229: 1553-1565.

[62] MorabitoC, SecchiF, SchubertA. Grapevine TPS (trehalose-6-phosphate synthase) family genes are differentially regulated during development, upon sugar treatment and drought stress. Plant Physiol Biochem, 2021, 164: 54-62.

[63] NwakaS, HolzerH. Molecular biology of trehalose and the trehalases in the yeast Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol, 1998, 58: 197-237.

[64] ParrouJL, EnjalbertB, PlourdeL, BaucheA, GonzalezB, FrançoisJ. Dynamic responses of reserve carbohydrate metabolism under carbon and nitrogen limitations in Saccharomyces cerevisiae. Yeast, 1999, 15: 191-203.

[65] PeetersK, van LeemputteF, FischerB, BoniniBM, QuezadaH, TsytlonokM, HaesenD, VanthienenW, BernardesN, Gonzalez-BlasCB, JanssensV, TompaP, VerséesW, TheveleinJM. Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras. Nat Commun, 2017, 8: 922.

[66] PonnuJ, SchlerethA, ZacharakiV, DziałoMA, AbelC, FeilR, SchmidM, WahlV. The trehalose 6-phosphate pathway impacts vegetative phase change in Arabidopsis thaliana. Plant J, 2020, 104: 768-780.

[67] PuttikamonkulS, WillgerSD, GrahlN, PerfectJR, MovahedN, BothnerB, ParkS, PaderuP, PerlinDS, CramerRAJr. Trehalose 6-phosphate phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus. Mol Microbiol, 2010, 77: 891-911.

[68] QiuL, WeiXY, WangSJ, WangJJ. Characterization of trehalose-6-phosphate phosphatase in trehalose biosynthesis, asexual development, stress resistance and virulence of an insect mycopathogen. Pestic Biochem Physiol, 2020, 163: 185-192.

[69] QuQ, LeeSJ, BoosW. TreT, a novel trehalose glycosyltransferring synthase of the hyperthermophilic archaeon Thermococcus litoralis. J Biol Chem, 2004, 279: 47890-47897.

[70] RamonM, de SmetI, VandesteeneL, NaudtsM, LeymanB, van DijckP, RollandF, BeeckmanT, TheveleinJM. Extensive expression regulation and lack of heterologous enzymatic activity of the class II trehalose metabolism proteins from Arabidopsis thaliana. Plant Cell Environ, 2009, 32: 1015-1032.

[71] ReicheltN, KorteA, KrischkeM, MuellerMJ, MaagD. Natural variation of warm temperature-induced raffinose accumulation identifies trehalose-6-phosphate synthase 1 as a modulator of thermotolerance. Plant Cell Environ, 2023, 46: 3392-3404.

[72] RichardsAB, KrakowkaS, DexterLB, SchmidH, WolterbeekAP, Waalkens-BerendsenDH, ShigoyukiA, KurimotoM. Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol, 2002, 40: 871-898.

[73] SadybekovAV, KatritchV. Computational approaches streamlining drug discovery. Nature, 2023, 616: 673-685.

[74] SakaguchiM. Diverse and common features of trehalases and their contributions to microbial trehalose metabolism. Appl Microbiol Biotechnol, 2020, 104: 1837-1847.

[75] Satoh-NagasawaN, NagasawaN, MalcomberS, SakaiH, JacksonD. A trehalose metabolic enzyme controls inflorescence architecture in maize. Nature, 2006, 441: 227-230.

[76] SchluepmannH, PellnyT, van DijkenA, SmeekensS, PaulM. Trehalose 6-phosphate is indispensable for carbohydrate utilization and growth in Arabidopsis thaliana. Proc Natl Acad Sci U S A, 2003, 100: 6849-6854.

[77] SchluepmannH, van DijkenA, AghdasiM, WobbesB, PaulM, SmeekensS. Trehalose mediated growth inhibition of Arabidopsis seedlings is due to trehalose-6-phosphate accumulation. Plant Physiol, 2004, 135: 879-890.

[78] SongXS, LiHP, ZhangJB, SongB, HuangT, DuXM, GongAD, LiuYK, FengYN, AgboolaRS, LiaoYC. Trehalose 6-phosphate phosphatase is required for development, virulence and mycotoxin biosynthesis apart from trehalose biosynthesis in Fusarium graminearum. Fungal Genet Biol, 2014, 63: 24-41.

[79] TangB, WangS, WangSG, WangHJ, ZhangJY, CuiSY. Invertebrate trehalose-6-phosphate synthase gene: genetic architecture, biochemistry, physiological function, and potential applications. Front Physiol, 2018, 9: 30.

[80] UhlandK, MondiglerM, SpiessC, PrinzW, EhrmannM. Determinants of translocation and folding of TreF, a trehalase of Escherichia coli. J Biol Chem, 2000, 275: 23439-23445.

[81] van DijckP, de RopL, SzlufcikK, van AelE, TheveleinJM. Disruption of the Candida albicans TPS2 gene encoding trehalose-6-phosphate phosphatase decreases infectivity without affecting hypha formation. Infect Immun, 2002, 70: 1772-1782.

[82] van DijkenAJ, SchluepmannH, SmeekensSC. Arabidopsis trehalose-6-phosphate synthase 1 is essential for normal vegetative growth and transition to flowering. Plant Physiol, 2004, 135: 969-977.

[83] VanapornM, TitballRW. Trehalose and Bacterial Virulence. Virulence, 2020, 11: 1192-1202.

[84] VandesteeneL, RamonM, Le RoyK, van DijckP, RollandF. A single active trehalose-6-P synthase (TPS) and a family of putative regulatory TPS-like proteins in Arabidopsis. Mol Plant, 2010, 3: 406-419.

[85] VicenteRL, SpinaL, GómezJPL, DejeanS, ParrouJL, FrançoisJM. Trehalose-6-phosphate promotes fermentation and glucose repression in Saccharomyces cerevisiae. Microb Cell, 2018, 5: 444-459.

[86] VogelG, AeschbacherRA, MüllerJ, BollerT, WiemkenA. Trehalose-6-phosphate phosphatases from Arabidopsis thaliana: identification by functional complementation of the yeast tps2 mutant. Plant J, 1998, 13: 673-683.

[87] VogelG, FiehnO, Jean-Richard-dit-BresselL, BollerT, WiemkenA, AeschbacherRA, WinglerA. Trehalose metabolism in Arabidopsis: occurrence of trehalose and molecular cloning and characterization of trehalose-6-phosphate synthase homologues. J Exp Bot, 2001, 52: 1817-1826.

[88] WahlV, PonnuJ, SchlerethA, ArrivaultS, LangeneckerT, FrankeA, FeilR, LunnJE, StittM, SchmidM. Regulation of flowering by trehalose-6-phosphate signaling in Arabidopsis thaliana. Science, 2013, 339: 704-707.

[89] WangG, GouY, GuoS, ZhouJJ, LiuC. RNA interference of trehalose-6-phosphate synthase and trehalase genes regulates chitin metabolism in two color morphs of Acyrthosiphon pisum Harris. Sci Rep, 2021, 11: 948.

[90] WangJ, FanH, LiY, ZhangTF, LiuYH. Trehalose-6-phosphate phosphatases are involved in trehalose synthesis and metamorphosis in Bactrocera minax. Insect Sci, 2022, 29: 1643-1658.

[91] WangX, WangM, HuangY, ZhuP, QianG, ZhangY, LiuY, ZhouJ, LiL. Genome-wide identification and analysis of stress response of trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase genes in quinoa. Int J Mol Sci, 2023, 2486950.

[92] WannetWJ, Op den CampHJ, WisselinkHW, van der DriftC, van GriensvenLJ, VogelsGD. Purification and characterization of trehalose phosphorylase from the commercial mushroom Agaricus bisporus. Biochim Biophys Acta, 1998, 1425: 177-188.

[93] WilsonRA, JenkinsonJM, GibsonRP, LittlechildJA, WangZY, TalbotNJ. Tps1 regulates the pentose phosphate pathway, nitrogen metabolism and fungal virulence. EMBO J, 2007, 26: 3673-3685.

[94] WilsonRA, GibsonRP, QuispeCF, LittlechildJA, TalbotNJ. An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus. Proc Natl Acad Sci U S A, 2010, 107: 21902-21907.

[95] WinglerA, DelatteTL, O'HaraLE, PrimavesiLF, JhurreeaD, PaulMJ, SchluepmannH. Trehalose 6-phosphate is required for the onset of leaf senescence associated with high carbon availability. Plant Physiol, 2012, 158: 1241-1251.

[96] WolschekMF, KubicekCP. The filamentous fungus Aspergillus niger contains two "differentially regulated" trehalose-6-phosphate synthase-encoding genes, tpsA and tpsB. J Biol Chem, 1997, 272: 2729-2735.

[97] XiongKC, WangJ, LiJH, DengYQ, PuP, FanH, LiuYH. RNA interference of a trehalose-6-phosphate synthase gene reveals its roles during larval-pupal metamorphosis in Bactrocera minax (Diptera: Tephritidae). J Insect Physiol, 2016, 91–92: 84-92.

[98] XueY, ShuiG, WenkMR. TPS1 drug design for rice blast disease in Magnaporthe oryzae. Springerplus, 2014, 3: 18.

[99] YadavUP, IvakovA, FeilR, DuanGY, WaltherD, GiavaliscoP, PiquesM, CarilloP, HubbertenHM, StittM, LunnJE. The sucrose–trehalose 6-phosphate (T6P) nexus: specificity and mechanisms of sucrose signaling by T6P. J Exp Bot, 2014, 65: 1051-1068.

[100] ZacharakiV, PonnuJ, CrepinN, LangeneckerT, HagmannJ, SkorzinskiN, Musialak-LangeM, WahlV, RollandF, SchmidM. Impaired KIN10 function restores developmental defects in the Arabidopsis trehalose 6-phosphate synthase1 (tps1) mutant. New Phytol, 2022, 235: 220-233.

[101] ZangB, LiH, LiW, DengXW, WangX. Analysis of trehalose-6-phosphate synthase (TPS) gene family suggests the formation of TPS complexes in rice. Plant Mol Biol, 2011, 76: 507-522.

[102] ZaragozaO, BlazquezMA, GancedoC. Disruption of the Candida albicans TPS1 gene encoding trehalose-6-phosphate synthase impairs formation of hyphae and decreases infectivity. J Bacteriol, 1998, 180: 3809-3815.

[103] ZhaiZ, LiuH, ShanklinJ. Phosphorylation of WRINKLED1 by KIN10 results in its proteasomal degradation, providing a link between energy homeostasis and lipid biosynthesis. Plant Cell, 2017, 29: 871-889.

[104] ZhaiZ, KeereetaweepJ, LiuH, FeilR, LunnJE, ShanklinJ. Trehalose 6-phosphate positively regulates fatty acid synthesis by stabilizing WRINKLED1. Plant Cell, 2018, 30: 2616-2627.

[105] ZhangK, YangX, WangY, YuY, HuangN, LiG, LiX, WuJC, YangS. Artificial intelligence in drug development. Nat Med, 2025, 31: 45-59.

[106] ZhangQ, ZhangM, ZhaoYQ, HuH, HuangYX, JiaGX. Identification of trehalose-6-phosphate synthase (TPS)-coding genes involved in flowering induction of Lilium× formolongi. Plant Physiol Biochem, 2022, 171: 84-94.

[107] ZhangY, PrimavesiLF, JhurreeaD, AndralojcPJ, MitchellRA, PowersSJ, SchluepmannH, DelatteT, WinglerA, PaulMJ. Inhibition of SNF1-related protein kinase1 activity and regulation of metabolic pathways by trehalose-6-phosphate. Plant Physiol, 2009, 149: 1860-1871.

[108] ZhouB, FangY, XiaoX, YangJ, QiJ, QiQ, FanY, TangC. Trehalose 6-phosphate/SnRK1 signaling participates in harvesting-stimulated rubber production in the hevea tree. Plants (Basel), 2022, 11212879.

Funding

National Natural Science Foundation of China(32172642)

Central Public-interest Scientific Institution Basal Research Fund

RIGHTS & PERMISSIONS

The Author(s)