A Moonlighting Enzyme Links <i>Escherichia coli</i> Cell Size with Central Metabolism

Growth rate and nutrient availability are the primary determinants of size in single-celled organisms: rapidly growing Escherichia coli cells are more than twice as large as their slow growing counterparts. Here we report the identification of the glucosyltransferase OpgH as a nutrient-dependent regulator of E. coli cell size. During growth under nutrient-rich conditions, OpgH localizes to the nascent septal site, where it antagonizes assembly of the tubulin-like cell division protein FtsZ, delaying division and increasing cell size. Biochemical analysis is consistent with OpgH sequestering FtsZ from growing polymers. OpgH is functionally analogous to UgtP, a Bacillus subtilis glucosyltransferase that inhibits cell division in a growth rate-dependent fashion. In a striking example of convergent evolution, OpgH and UgtP share no homology, have distinct enzymatic activities, and appear to inhibit FtsZ assembly through different mechanisms. Comparative analysis of E. coli and B. subtilis reveals conserved aspects of growth rate regulation and cell size control that are likely to be broadly applicable. These include the conservation of uridine diphosphate glucose as a proxy for nutrient status and the use of moonlighting enzymes to couple growth rate-dependent phenomena to central metabolism.单细胞生物的细胞体积主要由生长速率与营养可获得性决定：快速生长的大肠杆菌（Escherichia coli）细胞体积是慢速生长对应菌株的两倍以上。本研究报道了糖基转移酶（glucosyltransferase）OpgH作为大肠杆菌细胞体积营养依赖性调控因子的鉴定结果。在营养丰富的条件下生长时，OpgH会定位至新生隔膜位点，在此处拮抗微管蛋白样细胞分裂蛋白FtsZ（FtsZ）的组装，延迟细胞分裂并增大细胞体积。生化分析结果与OpgH从正在延伸的聚合物中隔离FtsZ的机制相符。OpgH在功能上与枯草芽孢杆菌（Bacillus subtilis）的糖基转移酶UgtP类似，后者可依生长速率依赖性方式抑制细胞分裂。在一个典型的趋同进化（convergent evolution）案例中，OpgH与UgtP并无同源性，二者具有不同的酶促活性，且似乎通过不同机制抑制FtsZ组装。对大肠杆菌与枯草芽孢杆菌的比较分析揭示了生长速率调控与细胞体积控制的保守特征，这些特征大概率具有广泛普适性。其中包括以尿苷二磷酸葡萄糖（uridine diphosphate glucose）作为营养状态的指示分子，以及利用兼职酶（moonlighting enzymes）将生长速率依赖性现象与中心代谢过程偶联。