If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: trehalose biosynthesis
|Superclasses:||Biosynthesis → Carbohydrates Biosynthesis → Sugars Biosynthesis → Trehalose Biosynthesis|
|Biosynthesis → Other Biosynthesis → Organic Solutes Biosynthesis → Trehalose Biosynthesis|
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-glucopyranosil 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 only when exposed to osmotic stress [Larsen87]. 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. The genes encoding the two enzymes, otsA and otsB, are both osmotically regulated. Transcription from these genes increases during osmotic stress [Giaever88] 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].
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
Horlacher96: 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
Larsen87: 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
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
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, 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
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
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
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
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
Seo00: Seo HS, Koo YJ, Lim JY, Song JT, Kim CH, Kim JK, Lee JS, Choi YD (2000). "Characterization of a bifunctional enzyme fusion of trehalose-6-phosphate synthetase and trehalose-6-phosphate phosphatase of Escherichia coli." Appl Environ Microbiol 66(6);2484-90. PMID: 10831428
Stoebel09: Stoebel DM, Hokamp K, Last MS, Dorman CJ (2009). "Compensatory evolution of gene regulation in response to stress by Escherichia coli lacking RpoS." PLoS Genet 5(10);e1000671. PMID: 19798444
Weber06a: Weber A, Kogl SA, Jung K (2006). "Time-dependent proteome alterations under osmotic stress during aerobic and anaerobic growth in Escherichia coli." J Bacteriol 188(20);7165-75. PMID: 17015655
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