Departments of Biological Chemistry and Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Microbiology (Reading). 2011 Jun;157(Pt 6):1565-1572. doi: 10.1099/mic.0.044263-0. Epub 2011 Apr 7.
Glycogen, a large α-glucan, is a ubiquitous energy storage molecule among bacteria, and its biosynthesis by the classical GlgC-GlgA pathway and its degradation have long been well understood - or so we thought. A second pathway of α-glucan synthesis, the four-step GlgE pathway, was recently discovered in mycobacteria. It requires trehalose as a precursor, and has been genetically validated as a novel anti-tuberculosis drug target. The ability to convert glycogen into trehalose was already known, so the GlgE pathway provides a complementary way of cycling these two metabolites. As well as containing cytosolic storage glycogen, mycobacteria possess an outer capsule containing a glycogen-like α-glucan that is implicated in immune system evasion, so the GlgE pathway might be linked to capsular α-glucan biosynthesis. Another pathway (the Rv3032 pathway) for α-glucan biosynthesis in mycobacteria generates a methylglucose lipopolysaccharide thought to be associated with fatty acid metabolism. A comparative genomic analysis was carried out to evaluate the occurrence and role of the classical pathway, the new GlgE pathway and the Rv3032 pathway across bacteria occupying very different ecological niches. The GlgE pathway is represented in 14 % of sequenced genomes from diverse bacteria (about half as common as the classical pathway), while the Rv3032 pathway is restricted with few exceptions to mycobacteria, and the GlgB branching enzyme, usually presumed to be associated with the classical pathway, correlates more strongly with the new GlgE pathway. The microbiological implications of recent discoveries in the light of the comparative genomic analysis are discussed.
糖原是一种广泛存在于细菌中的大型α-葡聚糖，其生物合成由经典的 GlgC-GlgA 途径及其降解途径长期以来得到了很好的理解——或者我们是这么认为的。最近在分枝杆菌中发现了第二种α-葡聚糖合成途径，即四步 GlgE 途径。它需要海藻糖作为前体，并已通过遗传验证为新型抗结核药物靶点。将糖原转化为海藻糖的能力早已为人所知，因此 GlgE 途径为这两种代谢物的循环提供了一种补充途径。除了含有细胞质储存糖原外，分枝杆菌还含有一种含有类似糖原的α-葡聚糖的外壳，该葡聚糖与免疫系统逃避有关，因此 GlgE 途径可能与外壳α-葡聚糖的生物合成有关。分枝杆菌中另一种α-葡聚糖生物合成途径（Rv3032 途径）生成一种甲基葡萄糖脂多糖，据信与脂肪酸代谢有关。进行了比较基因组分析，以评估经典途径、新的 GlgE 途径和 Rv3032 途径在占据非常不同生态位的细菌中的发生和作用。GlgE 途径存在于来自不同细菌的 14%测序基因组中（大约是经典途径的一半常见），而 Rv3032 途径除了少数例外，主要局限于分枝杆菌，而 GlgB 分支酶，通常被认为与经典途径有关，与新的 GlgE 途径相关性更强。根据比较基因组分析，讨论了最近在微生物学方面的发现的意义。
