De Smet Koen A L, Weston Anthony, Brown Ivor N, Young Douglas B, Robertson Brian D
Department of Infectious Diseases and Microbiology, Imperial College School of Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK1.
Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, UK2.
Microbiology (Reading). 2000 Jan;146 ( Pt 1):199-208. doi: 10.1099/00221287-146-1-199.
Trehalose is present as a free disaccharide in the cytoplasm of mycobacteria and as a component of cell-wall glycolipids implicated in tissue damage associated with mycobacterial infection. To obtain an overview of trehalose metabolism, we analysed data from the Mycobacterium tuberculosis genome project and identified ORFs with homology to genes encoding enzymes from three trehalose biosynthesis pathways previously characterized in other bacteria. Functional assays using mycobacterial extracts and recombinant enzymes derived from these ORFs demonstrated that mycobacteria can produce trehalose from glucose 6-phosphate and UDP-glucose (the OtsA-OtsB pathway) from glycogen-like alpha(1-->4)-linked glucose polymers (the TreY-TreZ pathway) and from maltose (the TreS pathway). Each of the pathways was found to be active in both rapid-growing Mycobacterium smegmatis and slow-growing Mycobacterium bovis BCG. The presence of a disrupted treZ gene in Mycobacterium leprae suggests that this pathway is not functional in this organism. The presence of multiple biosynthetic pathways indicates that trehalose plays an important role in mycobacterial physiology.
海藻糖在分枝杆菌的细胞质中以游离二糖的形式存在，并且作为细胞壁糖脂的一个组分，与分枝杆菌感染相关的组织损伤有关。为了全面了解海藻糖代谢，我们分析了结核分枝杆菌基因组计划的数据，并鉴定出与先前在其他细菌中表征的三种海藻糖生物合成途径的酶编码基因具有同源性的开放阅读框（ORF）。使用分枝杆菌提取物和源自这些ORF的重组酶进行的功能测定表明，分枝杆菌可以从6-磷酸葡萄糖和UDP-葡萄糖（OtsA-OtsB途径）、从糖原样α(1→4)-连接的葡萄糖聚合物（TreY-TreZ途径）以及从麦芽糖（TreS途径）产生海藻糖。发现每条途径在快速生长的耻垢分枝杆菌和缓慢生长的牛型结核分枝杆菌卡介苗中均有活性。麻风分枝杆菌中treZ基因的破坏表明该途径在该生物体中无功能。多种生物合成途径的存在表明海藻糖在分枝杆菌生理学中起重要作用。
