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Chapter 18 : Genetics of Mycobacterial Trehalose Metabolism

Authors: Rainer Kalscheuer1, Hendrik Koliwer-brandl2
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Affiliations: 1: Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany; 2: Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
Content Type: Monograph
Publication Year: 2014

Category: Microbial Genetics and Molecular Biology

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Abstract:

Trehalose is a natural nonreducing glucose disaccharide comprising an α,α-1,1-glycosidic linkage [α--glucopyranosyl-(1→1)-α--glucopyranoside]. The discovery of trehalose is credited to H. A. L. Wiggers (1832), who isolated a nonreducing sugar-like substance from the ergot fungus () of rye. Later this sugar was chemically characterized by Mitscherlich (1857), who termed it “mycose.” About the same time (1858), the French chemist M. Berthelot isolated and characterized a sugar substance from “trehala manna,” the sweet-tasting cocoon from the lepidopterous beetle , and coined the term “trehalose.” In 1876, M. A. Müntz found that trehalose and mycose were identical (see reference for an overview of the historical perspective). Since then, it has become clear that trehalose is a truly ubiquitous molecule that is synthesized by many different organisms including bacteria, yeasts, fungi, plants, and invertebrates. In the early days, trehalose was believed to exclusively serve as a carbon storage compound. Trehalose is nontoxic and, thus, accumulation to high intracellular concentrations is well tolerated. From this depot, glucose can rapidly be mobilized by hydrolysis mediated by the enzyme trehalase.

Citation: Kalscheuer R, Koliwer-brandl H. 2014. Genetics of Mycobacterial Trehalose Metabolism, p 361-375. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0002-2013
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Genetics of Mycobacterial Trehalose Metabolism
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Citation: Kalscheuer R, Koliwer-brandl H. 2014. Genetics of Mycobacterial Trehalose Metabolism, p 361-375. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0002-2013
/content/10.1128/9781555818845.chap18.fig18-1
Figure 1
Trehalose biosynthesis pathways in mycobacteria. Trehalose is synthesized either from glycolytic intermediates via the OtsA-OtsB pathway or from alpha-glucans via the TreY-TreZ pathway. UDP-glucose is formed from glucose-1-phosphate by the UTP-glucose-1-phosphate uridylyltransferase GalU (not depicted). This reaction, however, is not specific for trehalose biosynthesis.
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Figure 1

Trehalose biosynthesis pathways in mycobacteria. Trehalose is synthesized either from glycolytic intermediates via the OtsA-OtsB pathway or from alpha-glucans via the TreY-TreZ pathway. UDP-glucose is formed from glucose-1-phosphate by the UTP-glucose-1-phosphate uridylyltransferase GalU (not depicted). This reaction, however, is not specific for trehalose biosynthesis.

Citation: Kalscheuer R, Koliwer-brandl H. 2014. Genetics of Mycobacterial Trehalose Metabolism, p 361-375. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0002-2013
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Figure 2
Structure of the cord factor trehalose-6,6′-dimycolate. In this example, cyclopropanated alpha- and ketomycolates are illustrated.
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Figure 2

Structure of the cord factor trehalose-6,6′-dimycolate. In this example, cyclopropanated alpha- and ketomycolates are illustrated.

Citation: Kalscheuer R, Koliwer-brandl H. 2014. Genetics of Mycobacterial Trehalose Metabolism, p 361-375. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0002-2013
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Figure 3
Biosynthesis of the major sulfolipid SL-1 and of polyacyltrehalose (PAT). The synthesis of SL-1 and PAT is initiated by sulfation or acylation, respectively, at the 2-position of trehalose. The proposed reaction steps are depicted. Molecular organization of the SL-1 and PAT biosynthesis gene clusters in .
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Figure 3

Biosynthesis of the major sulfolipid SL-1 and of polyacyltrehalose (PAT). The synthesis of SL-1 and PAT is initiated by sulfation or acylation, respectively, at the 2-position of trehalose. The proposed reaction steps are depicted. Molecular organization of the SL-1 and PAT biosynthesis gene clusters in .

Citation: Kalscheuer R, Koliwer-brandl H. 2014. Genetics of Mycobacterial Trehalose Metabolism, p 361-375. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0002-2013
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Figure 4
Model of trehalose as a carrier molecule for mycolic acids in the fomation of the mycobacterial cell wall. Mycolic acids synthesized in the cytoplasm are first conjugated to trehalose and then exported as TMM via the transporter MmpL3. Extracellularly, TMM serves as the substrate of the antigen 85 complex comprising the mycolyltransferases FbpA-C, which transfer the mycolate moiety either to the arabinogalactan layer or to another TMM molecule, yielding cell-wall-bound mycolates or TDM, respectively. The released trehalose moiety of TMM is recycled by the ABC transporter LpqY-SugABC. A putative porin might facilitate transport across the mycomembrane for uptake of exogenous trehalose.
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Figure 4

Model of trehalose as a carrier molecule for mycolic acids in the fomation of the mycobacterial cell wall. Mycolic acids synthesized in the cytoplasm are first conjugated to trehalose and then exported as TMM via the transporter MmpL3. Extracellularly, TMM serves as the substrate of the antigen 85 complex comprising the mycolyltransferases FbpA-C, which transfer the mycolate moiety either to the arabinogalactan layer or to another TMM molecule, yielding cell-wall-bound mycolates or TDM, respectively. The released trehalose moiety of TMM is recycled by the ABC transporter LpqY-SugABC. A putative porin might facilitate transport across the mycomembrane for uptake of exogenous trehalose.

Citation: Kalscheuer R, Koliwer-brandl H. 2014. Genetics of Mycobacterial Trehalose Metabolism, p 361-375. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0002-2013
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Figure 5
Conversion of trehalose to alpha-glucans. Trehalose is reversibly interconverted by the trehalose synthase TreS to α-maltose, which is subsequently phosphorylated to α-maltose-1-phosphate by the maltokinase Pep2. Maltose-1-phosphate serves as the activated donor substrate for the maltosyltransferase GlgE producing linear α-1,4-glucans by elongating the nonreducing end of an α-glucan acceptor molecule. Finally, the branching enzyme GlgB introduces α-1,6-linked branches into the linear molecule.
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Figure 5

Conversion of trehalose to alpha-glucans. Trehalose is reversibly interconverted by the trehalose synthase TreS to α-maltose, which is subsequently phosphorylated to α-maltose-1-phosphate by the maltokinase Pep2. Maltose-1-phosphate serves as the activated donor substrate for the maltosyltransferase GlgE producing linear α-1,4-glucans by elongating the nonreducing end of an α-glucan acceptor molecule. Finally, the branching enzyme GlgB introduces α-1,6-linked branches into the linear molecule.

Citation: Kalscheuer R, Koliwer-brandl H. 2014. Genetics of Mycobacterial Trehalose Metabolism, p 361-375. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0002-2013
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