Flux through trehalose synthase flows from trehalose to the alpha anomer of maltose in mycobacteria

Miah, Farzana, Koliwer-Brandl, Hendrik, Rejzek, Martin, Field, Robert A. ORCID: https://orcid.org/0000-0001-8574-0275, Kalscheuer, Rainer and Bornemann, Stephen (2013) Flux through trehalose synthase flows from trehalose to the alpha anomer of maltose in mycobacteria. Chemistry and Biology, 20 (4). pp. 487-493. ISSN 1074-5521

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Abstract

Trehalose synthase (TreS) was thought to catalyze flux from maltose to trehalose, a precursor of essential trehalose mycolates in mycobacterial cell walls. However, we now show, using a genetic approach, that TreS is not required for trehalose biosynthesis in Mycobacterium smegmatis, whereas two alternative trehalose-biosynthetic pathways (OtsAB and TreYZ) are crucial. Consistent with this direction of flux, trehalose levels in Mycobacterium tuberculosis decreased when TreS was overexpressed. In addition, TreS was shown to interconvert the α anomer of maltose and trehalose using 1H and 19F-nuclear magnetic resonance spectroscopies using its normal substrates and deoxyfluoromaltose analogs, with the nonenzymatic mutarotation of α/β-maltose being slow. Therefore, flux through TreS in mycobacteria flows from trehalose to α-maltose, which is the appropriate anomer for maltose kinase of the GlgE α-glucan pathway, which in turn contributes to intracellular and/or capsular polysaccharide biosynthesis.

Item Type: Article
Additional Information: Funding Information: This work was supported by the United Kingdom Biotechnology and Biological Sciences Research Council (Doctoral Training Grant [BB/F017294/1] and Institute Strategic Programme Grant [BB/J004561/1]), the John Innes Foundation, the Strategic Research Fund of the Heinrich-Heine-University Düsseldorf, and the Jürgen Manchot Foundation. We thank Karl Syson for practical assistance and useful discussion, Shirley Fairhurst for assistance with the NMR spectroscopy, and Krit Tantanarat for kindly providing deoxyfluoromaltose analogs.
Uncontrolled Keywords: biochemistry,molecular medicine,molecular biology,pharmacology,drug discovery,clinical biochemistry,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School:
Faculty of Science > School of Biological Sciences
Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
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Depositing User: LivePure Connector
Date Deposited: 04 Sep 2024 13:36
Last Modified: 25 Sep 2024 18:06
URI: https://ueaeprints.uea.ac.uk/id/eprint/96547
DOI: 10.1016/j.chembiol.2013.02.014

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