title: Flux through trehalose synthase flows from trehalose to the alpha anomer of maltose in mycobacteria.
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 (1)H and (19)F-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.
authors.affiliation: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, Norfolk NR4 7UH, UK.
authors.forename: Farzana
authors.initials: F
authors.lastname: Miah
authors.forename: Hendrik
authors.initials: H
authors.lastname: Koliwer-Brandl
authors.forename: Martin
authors.initials: M
authors.lastname: Rejzek
authors.forename: Robert A
authors.initials: RA
authors.lastname: Field
authors.forename: Rainer
authors.initials: R
authors.lastname: Kalscheuer
authors.forename: Stephen
authors.initials: S
authors.lastname: Bornemann
mesh_terms: D002473:Cell Wall / Q000378:metabolism; D005964:Glucosyltransferases / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008320:Maltose / Q000031:analogs & derivatives / Q000378:metabolism*; D020102:Mycobacterium smegmatis / Q000201:enzymology* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D014199:Trehalose / Q000378:metabolism*
chemical_list: D008320:Maltose; D014199:Trehalose; D005964:Glucosyltransferases; C099692:trehalose synthase; C023180:trehalose-6-phosphate synthase; D010744:Phosphoric Monoester Hydrolases