Although many prokaryotes have glycolysis alternatives, it’s considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP₇) levels. 5-InsP₇ levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.

尽管许多原核生物都有糖酵解替代方案，但它被认为是真核生物中唯一产生能量的葡萄糖分解代谢途径。在这里，我们设法创造了一种混合糖酵解酵母。随后，我们发现了一种由OCA5编码的肌醇焦磷酸酶，它可以通过调节 5-二磷酸肌醇 1,2,3,4,6-五磷酸 (5-InsP ₇ ) 水平来调节糖酵解和呼吸作用。5-InsP ₇水平可以调节参与糖酵解和呼吸的基因的表达，代表一种可以感知 ATP 水平和调节中心碳代谢的全球机制。杂交糖酵解酵母在过量葡萄糖条件下生长过程中不产生乙醇，可产生2.68 g/L的游离脂肪酸，这是在酿酒酵母摇瓶中报道的最高产量。这项研究证明了混合糖酵解酵母的重要性，并将 Oca5 确定为控制糖酵解和呼吸之间平衡的肌醇焦磷酸酶，这可能阐明肌醇焦磷酸在调节真核代谢中的作用。