Liu Nian, Vita Nicolas, Holmière Marion, Gagnot Séverine, Brasseur Gaël, de Philip Pascale, Pagès Sandrine, Perret Stéphanie, Fierobe Henri-Pierre
Aix Marseille Univ, CNRS LCB, Marseille, France.
Baylor College of Medicine, Houston, TX, USA.
Commun Biol. 2025 Mar 30;8(1):523. doi: 10.1038/s42003-025-07971-7.
In Ruminiclostridium cellulolyticum, the hexokinase and galactokinase were formerly shown to strongly prefer GTP over ATP, whereas the phosphofructokinase is PPi-dependent, suggesting an unconventional central carbon metabolism in this anaerobic bacterium. Herein, the characterization of all other kinases of this pivotal pathway led to the identification of their preferred NTP/NDP. The kinases involved in the first reactions, primarily functioning as NTP-consuming enzymes, appear to be GTP-dependent. In contrast, the enzymes catalyzing the downstream steps that mainly generate NTP, show no marked preference. Consequently, its central carbon metabolism appears essentially driven by GTP, whose cellular content nears that of ATP. Interestingly, in vivo reciprocal exchange of the GTP-dependent hexokinase in R. cellulolyticum by the ATP-dependent glucokinase from Escherichia coli and vice versa generates modified strains that still catabolize glucose and glucose disaccharides. Altogether our data suggest an unexpected diversity and flexibility in the functioning of this central pathway in bacteria.
在解纤维素瘤胃梭菌中，先前已表明己糖激酶和半乳糖激酶强烈偏好GTP而非ATP，而磷酸果糖激酶依赖焦磷酸（PPi），这表明这种厌氧细菌具有非常规的中心碳代谢。在此，对这一关键途径中所有其他激酶的特性进行表征，从而确定了它们偏好的核苷三磷酸/核苷二磷酸（NTP/NDP）。参与最初反应的激酶主要作为消耗NTP的酶，似乎依赖GTP。相反，催化主要产生NTP的下游步骤的酶没有明显偏好。因此，其中心碳代谢似乎主要由GTP驱动，其细胞内含量接近ATP。有趣的是，在体内用来自大肠杆菌的依赖ATP的葡萄糖激酶替换解纤维素瘤胃梭菌中依赖GTP的己糖激酶，反之亦然，会产生仍能分解代谢葡萄糖和葡萄糖二糖的修饰菌株。总之，我们的数据表明细菌中这一中心途径的功能存在意想不到的多样性和灵活性。
