Advertisement

Diverse and common features of trehalases and their contributions to microbial trehalose metabolism

Abstract

Trehalose is a stable disaccharide that consists of two glucose units linked primarily by an α,α-(1 → 1)-linkage, and it has been found in a wide variety of organisms. In these organisms, trehalose functions not only as a source of carbon energy but also as a protector against various stress conditions. In addition, this disaccharide is attractive for use in a wide range of applications due to its bioactivities. In trehalose metabolism, direct trehalose-hydrolyzing enzymes are known as trehalases, which have been reported for bacteria, archaea, and eukaryotes, and are classified into glycoside hydrolase 37 (GH37), GH65, and GH15 families according to the Carbohydrate-Active enZyme (CAZy) database. The catalytic domains (CDs) of these enzymes commonly share (α/α)6-barrel structures and have two amino acid residues, Asp and/or Glu, that function as catalytic residues in an inverting mechanism. In this review, I focus on diverse and common features of trehalases within different GH families and their contributions to microbial trehalose metabolism.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Adhav A, Harne S, Bhide A, Giri A, Gayathri P, Joshi R (2019) Mechanistic insights into enzymatic catalysis by trehalase from the insect gut endosymbiont Enterobacter cloacae. FEBS J 286:1700–1716. https://doi.org/10.1111/febs.14760

  2. Alblova M, Smidova A, Docekal V, Vesely J, Herman P, Obsilova V, Obsil T (2017) Molecular basis of the 14-3-3 protein-dependent activation of yeast neutral trehalase Nth1. Proc Natl Acad Sci U S A 114:E9811–E9820. https://doi.org/10.1073/pnas.1714491114

  3. Alblova M, Smidova A, Kalabova D, Lentini Santo D, Obsil T, Obsilova V (2019) Allosteric activation of yeast enzyme neutral trehalase by calcium and 14-3-3 protein. Physiol Res 68:147–160. https://doi.org/10.33549/physiolres.933950

  4. Aleshin AE, Feng PH, Honzatko RB, Reilly PJ (2003) Crystal structure and evolution of a prokaryotic glucoamylase. J Mol Biol 327:61–73. https://doi.org/10.1016/S0022-2836(03)00084-6

  5. Andersen C, Schiffler B, Charbit A, Benz R (2002) pH-induced collapse of the extracellular loops closes Escherichia coli maltoporin and allows the study of asymmetric sugar binding. J Biol Chem 277:41318–41325. https://doi.org/10.1074/jbc.M206804200

  6. Argüelles JC (2000) Physiological roles of trehalose in bacteria and yeasts: a comparative analysis. Arch Microbiol 174:217–124. https://doi.org/10.1007/s002030000192

  7. Avonce N, Mendoza-Vargas A, Morett E (2006) Iturriaga G (2006) Insights on the evolution of trehalose biosynthesis. BMC Evol Biol 6:109. https://doi.org/10.1186/1471-2148-6-109

  8. Barraza A, Sánchez F (2013) Trehalases: a neglected carbon metabolism regulator? Plant Signal Behav 8:e24778. https://doi.org/10.4161/psb.24778

  9. Benaroudj N, Lee DH, Goldberg AL (2001) Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J Biol Chem 276:24261–24267. https://doi.org/10.1074/jbc.M101487200

  10. Boos W, Ehmann U, Bremer E, Middendorf A, Postma P (1987) Trehalase of Escherichia coli. Mapping and cloning of its structural gene and identification of the enzyme as a periplasmic protein induced under high osmolarity growth conditions. J Biol Chem 262:13212–13218

  11. Carroll JD, Pastuszak I, Edavana VK, Pan YT, Elbein AD (2007) A novel trehalase from Mycobacterium smegmatis - purification, properties, requirements. FEBS J 274:1701–1714. https://doi.org/10.1111/j.1742-4658.2007.05715.x

  12. Chandra G, Chater KF, Bornemann S (2011) Unexpected and widespread connections between bacterial glycogen and trehalose metabolism. Microbiology 157:1565–1572. https://doi.org/10.1099/mic.0.044263-0

  13. Cheng Q, Gao H, Hu N (2016) A trehalase from Zunongwangia sp.: characterization and improving catalytic efficiency by directed evolution. BMC Biotechnol 16:9. https://doi.org/10.1186/s12896-016-0239-z

  14. d’Enfert C, Bonini BM, Zapella PD, Fontaine T, da Silva AM, Terenzi HF (1999) Neutral trehalases catalyse intracellular trehalose breakdown in the filamentous fungi Aspergillus nidulans and Neurospora crassa. Mol Microbiol 32:471–483. https://doi.org/10.1046/j.1365-2958.1999.01327.x

  15. Du J, Liang Y, Xu F, Sun B, Wang Z (2013) Trehalose rescues Alzheimer’s disease phenotypes in APP/PS1 transgenic mice. J Pharm Pharmacol 65:1753–1756. https://doi.org/10.1111/jphp.12108

  16. Eck R, Bergmann C, Ziegelbauer K, Schonfeld W, Kunkel W (1997) A neutral trehalase gene from Candida albicans: molecular cloning, characterization and disruption. Microbiology 143:3747–3756. https://doi.org/10.1099/00221287-143-12-3747

  17. Egloff MP, Uppenberg J, Haalck L, Tilbeurgh V (2001) Crystal structure of maltose phosphorylase from Lactobacillus brevis: unexpected evolutionary relationship with glucoamylases. Structure 9:689–697. https://doi.org/10.1016/S0969-2126(01)00626-8

  18. Elbein AD, Pan YT, Pastuszak I, Carroll D (2003) New insights on trehalose: a multifunctional molecule. Glycobiology 13:17–27. https://doi.org/10.1093/glycob/cwg047

  19. Eleutherio EC, Araujo PS, Panek AD (1993) Protective role of trehalose during heat stress in Saccharomyces cerevisiae. Cryobiology 30:591–596. https://doi.org/10.1006/cryo.1993.1061

  20. Eleutherio E, Panek A, De Mesquita JF, Trevisol E, Magalhães R (2015) Revisiting yeast trehalose metabolism. Curr Genet 61:263–274. https://doi.org/10.1007/s00294-014-0450-1

  21. Frandsen TP, Dupont C, Lehmbeck J, Stoffer B, Sierks MR, Honzatko RB, Svensson B (1994) Site-directed mutagenesis of the catalytic base glutamic acid 400 in glucoamylase from Aspergillus niger and of tyrosine 48 and glutamine 401, both hydrogen-bonded to the gamma-carboxylate group of glutamic acid 400. Biochemistry 33:13808–13816

  22. Gibson RP, Gloster TM, Roberts S, Warren RA, Storch de Gracia I, García A, Chiara JL, Davies GJ (2007) Molecular basis for trehalase inhibition revealed by the structure of trehalase in complex with potent inhibitors. Angew Chem Int Ed Eng 46:4115–4119. https://doi.org/10.1002/anie.200604825

  23. He S, Bystricky K, Leon S, François JM, Parrou JL (2009) The Saccharomyces cerevisiae vacuolar acid trehalase is targeted at the cell surface for its physiological function. FEBS J 276:5432–5446. https://doi.org/10.1111/j.1742-4658.2009.07227.x

  24. Herdeiro RS, Pereira MD, Panek AD, Eleutherio EC (2006) Trehalose protects Saccharomyces cerevisiae from lipid peroxidation during oxidative stress. Biochim Biophys Acta 1760:340–346. https://doi.org/10.1016/j.bbagen.2006.01.010

  25. Higashiyama T (2002) Novel functions and applications of trehalose. Pure Appl Chem 74:1263–1269. https://doi.org/10.1351/pac200274071263

  26. Horlacher R, Uhland K, Klein W, Ehrmann M, Boos W (1996) Characterization of a cytoplasmic trehalase of Escherichia coli. J Bacteriol 178:6250–6257. https://doi.org/10.1128/jb.178.21.6250-6257.1996

  27. Hottiger T, Schmutz P, Wiemken A (1987) Heat-induced accumulation and futile cycling of trehalose in Saccharomyces cerevisiae. J Bacteriol 169:5518–5522. https://doi.org/10.1128/jb.169.12.5518-5522.1987

  28. Huang J, Reggiori F, Klionsky DJ (2007) The transmembrane domain of acid trehalase mediates ubiquitin-independent multivesicular body pathway sorting. Mol Biol Cell 18:2511–2524. https://doi.org/10.1091/mbc.e06-11-0995

  29. Iturriaga G, Suárez R, Nova-Franco B (2009) Trehalose metabolism: from osmoprotection to signaling. Int J Mol Sci 10:3793–3810. https://doi.org/10.3390/ijms10093793

  30. Jarling M, Cauvet T, Grundmeier M, Kuhnert K, Pape H (2004) Isolation of mak1 from Actinoplanes missouriensis and evidence that Pep2 from Streptomyces coelicolor is a maltokinase. J Basic Microbiol 44:360–373. https://doi.org/10.1002/jobm.200410403

  31. Jules M, Beltran G, François J, Parrou JL (2008) New insights into trehalose metabolism by Saccharomyces cerevisiae: NTH2 encodes a functional cytosolic trehalase, and deletion of TPS1 reveals Ath1p-dependent trehalose mobilization. Appl Environ Microbiol 74:605–614. https://doi.org/10.1128/AEM.00557-07

  32. Kermani AA, Roy R, Gopalasingam C, Kocurek KI, Patel TR, Alderwick LJ, Besra GS, Fütterer K (2019) Crystal structure of the TreS:Pep2 complex, initiating α-glucan synthesis in the GlgE pathway of mycobacteria. J Biol Chem 294:7348–7359. https://doi.org/10.1074/jbc.RA118.004297

  33. Kim J, Alizadeh P, Harding T, Hefner-Gravink A, Klionsky DJ (1996) Disruption of the yeast ATH1 gene confers better survival after dehydration, freezing, and ethanol shock: potential commercial applications. Appl Environ Microbiol 62:1563–1569

  34. Kouril T, Zaparty M, Marrero J, Brinkmann H, Siebers B (2008) A novel trehalose synthesizing pathway in the hyperthermophilic Crenarchaeon Thermoproteus tenax: the unidirectional TreT pathway. Arch Microbiol 190:355–369. https://doi.org/10.1007/s00203-008-0377-3

  35. Kruger U, Wang Y, Kumar S, Mandelkow EM (2012) Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiol Aging 33:2291–2305. https://doi.org/10.1016/j.neurobiolaging.2011.11.009

  36. Lee J, Lee A, Moon K, Choi KH, Cha J (2018) Saci_1816: a trehalase that catalyzes trehalose degradation in the thermoacidophilic Crenarchaeon Sulfolobus acidocaldarius. J Microbiol Biotechnol 28:909–916. https://doi.org/10.4014/jmb.1802.02038

  37. Li H, Su H, Kim SB, Chang YK, Hong SK, Seo YG, Kim CJ (2012) Enhanced production of trehalose in Escherichia coli by homologous expression of otsBA in the presence of the trehalase inhibitor, validamycin A, at high osmolarity. J Biosci Bioeng 113:224–232. https://doi.org/10.1016/j.jbiosc.2011.09.018

  38. Li Z, Wei P, Cheng H, He P, Wang Q, Jiang N (2014) Functional role of β-domain in the Thermoanaerobacter tengcongensis glucoamylase. Appl Microbiol Biotechnol 98:2091–2099. https://doi.org/10.1007/s00253-013-5051-2

  39. Liu R, Barkhordarian H, Emadi S, Park CB, Sierks MR (2005) Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42. Neurobiol Dis 20:74–81. https://doi.org/10.1016/j.nbd.2005.02.003

  40. Magalhães RSS, Popova B, Braus GH, Outeiro TF, Eleutherio ECA (2018) The trehalose protective mechanism during thermal stress in Saccharomyces cerevisiae: the roles of Ath1 and Agt1. FEMS Yeast Res 18(6). https://doi.org/10.1093/femsyr/foy066

  41. Maicas S, Guirao-Abad JP, Argüelles JC (2016) Yeast trehalases: two enzymes, one catalytic mission. Biochim Biophys Acta 1860:2249–2254. https://doi.org/10.1016/j.bbagen.2016.04.020

  42. Mittenbühler K, Holzer H (1988) Purification and characterization of acid trehalase from the yeast suc2 mutant. J Biol Chem 263:8537–8543

  43. Mizunoe Y, Kobayashi M, Sudo Y, Watanabe S, Yasukawa H, Natori D, Hoshino A, Negishi A, Okita N, Komatsu M, Higami Y (2018) Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways. Redox Biol 15:115–124. https://doi.org/10.1016/j.redox.2017.09.007

  44. Moon JH, Lee W, Park J, Choi KH, Cha J (2016) Characterization of a trehalose-degrading enzyme from the hyperthermophilic archaeon Sulfolobus acidocaldarius. J Biosci Bioeng 122:47–51. https://doi.org/10.1016/j.jbiosc.2015.12.011

  45. Nakai H, Baumann MJ, Petersen BO, Westphal Y, Schols H, Dilokpimol A, Hachem MA, Lahtinen SJ, Duus JØ, Svensson B (2009) The maltodextrin transport system and metabolism in Lactobacillus acidophilus NCFM and production of novel alpha-glucosides through reverse phosphorolysis by maltose phosphorylase. FEBS J 276:7353–7365. https://doi.org/10.1111/j.1742-4658.2009.07445.x

  46. Nakai H, Petersen BO, Westphal Y, Dilokpimol A, Abou Hachem M, Duus JØ, Schols HA, Svensson B (2010) Rational engineering of Lactobacillus acidophilus NCFM maltose phosphorylase into either trehalose or kojibiose dual specificity phosphorylase Protein. Eng Des Sel 23:781–787. https://doi.org/10.1093/protein/gzq055

  47. Nwaka S, Holzer H (1998) Molecular biology of trehalose and the trehalases in the yeast Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol 58:197–237

  48. Nwaka S, Kopp M, Holzer H (1995) Expression and function of the trehalase genes NTH1 and YBR0106 in Saccharomyces cerevisiae. J Biol Chem 270:10193–10198. https://doi.org/10.1074/jbc.270.17.10193

  49. Nwaka S, Mechler B, Holzer H (1996) Deletion of the ATH1 gene in Saccharomyces cerevisiae prevents growth on trehalose. FEBS Lett 386:235–238. https://doi.org/10.1016/0014-5793(96)00450-4

  50. Ohnishi H, Matsumoto H, Sakai H, Ohta T (1994) Functional roles of Trp337 and Glu632 in Clostridium glucoamylase, as determined by chemical modification, mutagenesis, and the stopped-flow method. J Biol Chem 269:3503–3510

  51. Ohtake S, Wang YJ (2011) Trehalose: current use and future applications. J Pharm Sci 100:2020–2053. https://doi.org/10.1002/jps.22458

  52. Oku K, Watanabe H, Kubota M, Fukuda S, Kurimoto M, Tsujisaka Y, Komori M, Inoue Y, Sakurai M (2003) NMR and quantum chemical study on the OH...pi and CH...O interactions between trehalose and unsaturated fatty acids: implication for the mechanism of antioxidant function of trehalose. J Am Chem Soc 125:12739–12748. https://doi.org/10.1021/ja034777e

  53. Pan YT, Koroth Edavana V, Jourdian WJ, Edmondson R, Carroll JD, Pastuszak I, Elbein AD (2004) Trehalose synthase of Mycobacterium smegmatis: purification, cloning, expression, and properties of the enzyme. Eur J Biochem 271:4259–4269. https://doi.org/10.1111/j.1432-1033.2004.04365.x

  54. Pedreño Y, Maicas S, Argüelles JC, Sentandreu R, Valentin E (2004) The ATC1 gene encodes a cell wall-linked acid trehalase required for growth on trehalose in Candida albicans. J Biol Chem 279:40852–40860. https://doi.org/10.1074/jbc.M400216200

  55. Pedreño Y, González-Párraga P, Martínez-Esparza M, Sentandreu R, Valentín E, Argüelles JC (2007) Disruption of the Candida albicans ATC1 gene encoding a cell-linked acid trehalase decreases hypha formation and infectivity without affecting resistance to oxidative stress. Microbiology. 153:1372–1381. https://doi.org/10.1099/mic.0.2006/003921-0

  56. Plourde-Owobi L, Durner S, Parrou JL, Wieczorke R, Goma G, Francois J (1999) AGT1, encoding an alpha-glucoside transporter involved in uptake and intracellular accumulation of trehalose in Saccharomyces cerevisiae. J Bacteriol 181:3830–3832

  57. Portbury SD, Hare DJ, Sgambelloni C, Perronnes K, Portbury AJ, Finkelstein DI, Adlard PA (2017) Trehalose improves cognition in the transgenic Tg2576 mouse model of Alzheimer’s disease. J Alzheimers Dis 60:549–560. https://doi.org/10.3233/JAD-170322

  58. Purvis JE, Yomano LP, Ingram LO (2005) Enhanced trehalose production improves growth of Escherichia coli under osmotic stress. Appl Environ Microbiol 71:3761–3769. https://doi.org/10.1128/AEM.71.7.3761-3769.2005

  59. Qu Q, Lee SJ, Boos W (2004) TreT, a novel trehalose glycosyltransferring synthase of the hyperthermophilic archaeon Thermococcus litoralis. J Biol Chem 279:47890–47897. https://doi.org/10.1074/jbc.M404955200

  60. Roy R, Usha V, Kermani A, Scott DJ, Hyde EI, Besra GS, Alderwick LJ, Fütterer K (2013) Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2. ACS Chem Biol 8:2245–2255. https://doi.org/10.1021/cb400508k

  61. Ruhal R, Kataria R, Choudhury B (2013) Trends in bacterial trehalose metabolism and significant nodes of metabolic pathway in the direction of trehalose accumulation. Microb Biotechnol 6:493–502. https://doi.org/10.1111/1751-7915.12029

  62. Ryu SI, Park CS, Cha J, Woo EJ, Lee SB (2005) A novel trehalose-synthesizing glycosyltransferase from Pyrococcus horikoshii: molecular cloning and characterization. Biochem Biophys Res Commun 329:429–436. https://doi.org/10.1016/j.bbrc.2005.01.149

  63. Sakaguchi M, Shimodaira S, Ishida S, Amemiya M, Honda S, Sugahara Y, Oyama F, Kawakita M (2015) Identification of GH15 family thermophilic archaeal trehalases that function within a narrow acidic pH range. Appl Environ Microbiol 81:4920–4931. https://doi.org/10.1128/AEM.00956-15

  64. Sakaguchi M, Matsushima Y, Nagamine Y, Matsuhashi T, Honda S, Okuda S, Ohno M, Sugahara Y, Shin Y, Oyama F, Kawakita M (2017) Functional dissection of the N-terminal sequence of Clostridium sp. G0005 glucoamylase: identification of components critical for folding the catalytic domain and for constructing the active site structure. Appl Microbiol Biotechnol 101:2415–2425. https://doi.org/10.1007/s00253-016-8024-4

  65. Sánchez-Fresneda R, Martínez-Esparza M, Maicas S, Argüelles JC, Valentín E (2014) In Candida parapsilosis the ATC1 gene encodes for an acid trehalase involved in trehalose hydrolysis, stress resistance and virulence. PLoS One 9:e99113. https://doi.org/10.1371/journal.pone.0099113

  66. Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC (2007) Trehalose, a novel mTOR independent autophagy enhancer, accelerates the clearance of mutant huntingtin and α-synuclein. J Biol Chem 282:5641–5652. https://doi.org/10.1074/jbc.M609532200

  67. Sierks MR, Ford C, Reilly PJ, Svensson B (1990) Catalytic mechanism of fungal glucoamylase as defined by mutagenesis of Asp176, Glu179 and Glu180 in the enzyme from Aspergillus awamori. Protein Eng 3:193–198

  68. Singer MA, Lindquist S (1998) Thermotolerance in Saccharomyces cerevisiae: the Yin and Yang of trehalose. Trends Biotechnol 16:460–468

  69. Takayama K, Wang C, Besra GS (2005) Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 18:81–101. https://doi.org/10.1128/CMR.18.1.81-101.2005

  70. Thevelein JM (1984) Regulation of trehalose mobilization in fungi. Microbiol Rev 48:42–59

  71. Touhara KK, Nihira T, Kitaoka M, Nakai H, Fushinobu S (2014) Structural basis for reversible phosphorolysis and hydrolysis reactions of 2-O-α-glucosylglycerol phosphorylase. J Biol Chem 289:18067–18075. https://doi.org/10.1074/jbc.M114.573212

  72. Uhland K, Mondigler M, Spiess C, Prinz W, Ehrmann M (2000) Determinants of translocation and folding of TreF, a trehalase of Escherichia coli. J Biol Chem 275:23439–23445. https://doi.org/10.1074/jbc.M002793200

  73. Yuasa M, Okamura T, Kimura M, Honda S, Shin Y, Kawakita M, Oyama F, Sakaguchi M (2018) Two trehalose-hydrolyzing enzymes from Crenarchaeon Sulfolobus acidocaldarius exhibit distinct activities and affinities toward trehalose. Appl Microbiol Biotechnol 102:4445–4455. https://doi.org/10.1007/s00253-018-8915-7

  74. Zilli DM, Lopes RG, Alves SL Jr, Barros LM, Miletti LC, Stambuk BU (2015) Secretion of the acid trehalase encoded by the CgATH1 gene allows trehalose fermentation by Candida glabrata. Microbiol Res 179:12–19. https://doi.org/10.1016/j.micres.2015.06.008

Download references

Author information

Correspondence to Masayoshi Sakaguchi.

Ethics declarations

Conflict of interest

The author declares that he has no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 409 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sakaguchi, M. Diverse and common features of trehalases and their contributions to microbial trehalose metabolism. Appl Microbiol Biotechnol (2020) doi:10.1007/s00253-019-10339-7

Download citation

Keywords

  • Trehalase
  • Glycoside hydrolase (GH) family
  • GH15
  • GH37
  • GH65
  • Trehalose metabolism