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Escherichia coli K-12 substr. MG1655 Pathway: trehalose biosynthesis I
Inferred from experiment

Pathway diagram: trehalose biosynthesis I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Synonyms: trehalose biosynthesis

Superclasses: BiosynthesisCarbohydrates BiosynthesisSugars BiosynthesisTrehalose Biosynthesis
BiosynthesisMetabolic Regulators BiosynthesisOrganic Solutes BiosynthesisTrehalose Biosynthesis

General Background

The name trehalose was introduced in 1858 to describe a main constituent of shells that are secreted by various insects on tree leaves in the middle east. These shells were often dried and used as a sweetening agent, and are believed to be related to the biblical Manna, the food supplied to the Israelites in their journey through the wilderness of Arabia. One variety of these shells, produced by the beetles Larinus maculatus and Larinus nidificans, was called "trehala manna", and the sugar extracted from it was named trehalique glucose, or trehalose [Richards02]. In fact, trehalose is a disaccharide that is ubiquitous in the biosphere. It consists of two subunits of glucose bound by an α:1-1 linkage (α-D-glucopyranosyl α-D-glucopyranoside) and is thus nonreducing. Trehalose has been isolated and characterized from many prokaryotic and eukaryotic organisms, including bacteria, yeast, plants, insects and mammals [Arguelles00] (and original references described therein).

In addition to being nonreducing, trehalose possesses several unique properties, including high hydrophilicity, chemical stability, nonhygroscopic glass formation and no internal hydrogen bond formation. The combination of these features explains the principal role of trehalose as a stress metabolite.

About This Pathway

Under conditions of elevated osmotic strength, E. coli can regulate the osmotic strength of the cytoplasm by accumulating K+ ions and some organic molecules, commonly called osmoprotectants or compatible solutes. The preferred osmoprotectant of E. coli is glycine betaine. However, its synthesis relies on an external supply of proline, betaines, or choline. When these compounds are not available, a cell can achieve a moderate level of osmotic tolerance by accumulation of glutamate and trehalose [Styrvold91].

E. coli synthesizes and accumulates trehalose when exposed to osmotic stress [Larsen87a] and low temperatures [Kandror02]. It is synthesized from UDP-glucose and glucose-6-phosphate via trehalose-6-phosphate, by the action of two enzymes, trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase. Expression of both genes encoding the two enzymes, otsA and otsB, is osmotically regulated. Transcription from these genes increases during osmotic stress [Giaever88] and cold shock [Kandror02] and when the cells enter stationary phase, and requires the stress sigma factor RpoS [HenggeAronis91]. Synthesis of trehalose is also stimulated directly by K+ ion-dependent activation of trehalose-6-phosphate synthase enzyme [Giaever88].

Under osmotic stress, E. coli overproduces trehalose, some of which is excreted to the periplasmic space. Once there, it is degraded by the periplasmic trehalase (see trehalose degradation II (trehalase)). This process was named "a futile cycle for controlling the cytoplasmic level of trehalose" [Styrvold91].

Reviews: [Strom93, Elbein03, Ruhal13]

Created 08-Oct-1996 by Riley M, Marine Biological Laboratory
Revised 09-Feb-2005 by Caspi R, SRI International
Last-Curated 24-Dec-2014 by Keseler I, SRI International


Arguelles00: Arguelles JC (2000). "Physiological roles of trehalose in bacteria and yeasts: a comparative analysis." Arch Microbiol 174(4);217-24. PMID: 11081789

Elbein03: Elbein AD, Pan YT, Pastuszak I, Carroll D (2003). "New insights on trehalose: a multifunctional molecule." Glycobiology 13(4);17R-27R. PMID: 12626396

Giaever88: Giaever HM, Styrvold OB, Kaasen I, Strom AR (1988). "Biochemical and genetic characterization of osmoregulatory trehalose synthesis in Escherichia coli." J Bacteriol 1988;170(6);2841-9. PMID: 3131312

HenggeAronis91: Hengge-Aronis R, Klein W, Lange R, Rimmele M, Boos W (1991). "Trehalose synthesis genes are controlled by the putative sigma factor encoded by rpoS and are involved in stationary-phase thermotolerance in Escherichia coli." J Bacteriol 173(24);7918-24. PMID: 1744047

Horlacher96a: Horlacher R, Peist R, Boos W (1996). "Improved method for the preparative synthesis of labeled trehalose of high specific activity by Escherichia coli." Appl Environ Microbiol 62(10);3861-3. PMID: 8837441

Kandror02: Kandror O, DeLeon A, Goldberg AL (2002). "Trehalose synthesis is induced upon exposure of Escherichia coli to cold and is essential for viability at low temperatures." Proc Natl Acad Sci U S A 99(15);9727-32. PMID: 12105274

Larsen87a: Larsen PI, Sydnes LK, Landfald B, Strom AR (1987). "Osmoregulation in Escherichia coli by accumulation of organic osmolytes: betaines, glutamic acid, and trehalose." Arch Microbiol 147(1);1-7. PMID: 2883950

Richards02: Richards AB, Krakowka S, Dexter LB, Schmid H, Wolterbeek AP, Waalkens-Berendsen DH, Shigoyuki A, Kurimoto M (2002). "Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies." Food Chem Toxicol 40(7);871-98. PMID: 12065209

Ruhal13: 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(5);493-502. PMID: 23302511

Strom93: Strom AR, Kaasen I (1993). "Trehalose metabolism in Escherichia coli: stress protection and stress regulation of gene expression." Mol Microbiol 1993;8(2);205-10. PMID: 8391102

Styrvold91: Styrvold OB, Strom AR (1991). "Synthesis, accumulation, and excretion of trehalose in osmotically stressed Escherichia coli K-12 strains: influence of amber suppressors and function of the periplasmic trehalase." J Bacteriol 173(3);1187-92. PMID: 1825082

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Barria13: Barria C, Malecki M, Arraiano CM (2013). "Bacterial adaptation to cold." Microbiology 159(Pt 12);2437-43. PMID: 24068238

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Gibson02: Gibson RP, Lloyd RM, Charnock SJ, Davies GJ (2002). "Characterization of Escherichia coli OtsA, a trehalose-6-phosphate synthase from glycosyltransferase family 20." Acta Crystallogr D Biol Crystallogr 58(Pt 2);349-51. PMID: 11807274

Gibson02a: Gibson RP, Turkenburg JP, Charnock SJ, Lloyd R, Davies GJ (2002). "Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA." Chem Biol 9(12);1337-46. PMID: 12498887

Gibson04: Gibson RP, Tarling CA, Roberts S, Withers SG, Davies GJ (2004). "The donor subsite of trehalose-6-phosphate synthase: binary complexes with UDP-glucose and UDP-2-deoxy-2-fluoro-glucose at 2 A resolution." J Biol Chem 279(3);1950-5. PMID: 14570926

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Guo12: Guo W, Hao H, Dai M, Wang Y, Huang L, Peng D, Wang X, Wang H, Yao M, Sun Y, Liu Z, Yuan Z (2012). "Development of quinoxaline 1, 4-dioxides resistance in Escherichia coli and molecular change under resistance selection." PLoS One 7(8);e43322. PMID: 22952665

Joseph10: Joseph TC, Rajan LA, Thampuran N, James R (2010). "Functional characterization of trehalose biosynthesis genes from E. coli: an osmolyte involved in stress tolerance." Mol Biotechnol 46(1);20-5. PMID: 20217281

Kaasen92: Kaasen I, Falkenberg P, Styrvold OB, Strom AR (1992). "Molecular cloning and physical mapping of the otsBA genes, which encode the osmoregulatory trehalose pathway of Escherichia coli: evidence that transcription is activated by katF (AppR)." J Bacteriol 1992;174(3);889-98. PMID: 1310094

Kaasen94: Kaasen I, McDougall J, Strom AR (1994). "Analysis of the otsBA operon for osmoregulatory trehalose synthesis in Escherichia coli and homology of the OtsA and OtsB proteins to the yeast trehalose-6-phosphate synthase/phosphatase complex." Gene 145(1);9-15. PMID: 8045430

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Klein91: Klein W, Ehmann U, Boos W (1991). "The repression of trehalose transport and metabolism in Escherichia coli by high osmolarity is mediated by trehalose-6-phosphate phosphatase." Res Microbiol 1991;142(4);359-71. PMID: 1651549

Kong01: Kong X, Liu Y, Gou X, Zhang H, Wang X, Zhang J (2001). "Directed evolution of operon of trehalose-6-phosphate synthase/phosphatase from Escherichia coli." Biochem Biophys Res Commun 280(1);396-400. PMID: 11162529

Koonin94: Koonin EV, Tatusov RL (1994). "Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search." J Mol Biol 244(1);125-32. PMID: 7966317

KuczynskaWisnik14: Kuczynska-Wisnik D, Stojowska K, Matuszewska E, Leszczynska D, Moruno Algara M, Augustynowicz M, Laskowska E (2014). "Lack of intracellular trehalose affects formation of Escherichia coli persister cells." Microbiology. PMID: 25500492

Kuznetsova05: Kuznetsova E, Proudfoot M, Sanders SA, Reinking J, Savchenko A, Arrowsmith CH, Edwards AM, Yakunin AF (2005). "Enzyme genomics: Application of general enzymatic screens to discover new enzymes." FEMS Microbiol Rev 29(2);263-79. PMID: 15808744

Kuznetsova06: Kuznetsova E, Proudfoot M, Gonzalez CF, Brown G, Omelchenko MV, Borozan I, Carmel L, Wolf YI, Mori H, Savchenko AV, Arrowsmith CH, Koonin EV, Edwards AM, Yakunin AF (2006). "Genome-wide analysis of substrate specificities of the Escherichia coli haloacid dehalogenase-like phosphatase family." J Biol Chem 281(47):36149-61. PMID: 16990279

Lazarowski03: Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003). "Release of cellular UDP-glucose as a potential extracellular signaling molecule." Mol Pharmacol 63(5);1190-7. PMID: 12695547

Li12: 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(2);224-32. PMID: 22036231

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by Pathway Tools version 19.5 (software by SRI International) on Fri Apr 29, 2016, biocyc11.