北京化工大学Jens Nielsen和Zihe Liu共同合作，近期取得重要工作进展，他们研究发现通过糖酵解和呼吸的通量调节由酵母中的肌醇焦磷酸盐平衡。相关研究成果2023年2月8日在线发表于《细胞》杂志上。
据介绍，尽管许多原核生物有糖酵解的替代品，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。
研究人员成功地创造了一种混合糖酵解酵母。随后，他们鉴定了一种由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-InsP7）水平来调节糖酵解和呼吸。5-InsP7水平可以调节糖酵解和呼吸相关基因的表达，这是一种可以感知ATP水平并调节中枢碳代谢的总体机制。混合糖酵解酵母在过量葡萄糖下生长期间不产生乙醇，可产生2.68g/L的游离脂肪酸，这是酿酒酵母摇瓶中产量最高的。
总之，这项研究证明了混合糖酵解酵母的重要性，并确定Oca5是一种控制糖酵解和呼吸之间平衡的肌醇焦磷酸酶，这可能揭示了肌醇焦磷酸酶在调节真核代谢中的作用。
附：英文原文
Title: Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast
Author: Ning Qin, Lingyun Li, Xu Ji, Rui Pereira, Yu Chen, Shile Yin, Chaokun Li, Xiaozhen Wan, Danye Qiu, Junfeng Jiang, Hao Luo, Yueping Zhang, Genlai Dong, Yiming Zhang, Shuobo Shi, Henning J. Jessen, Jianye Xia, Yun Chen, Christer Larsson, Tianwei Tan, Zihe Liu, Jens Nielsen
Issue&Volume: 2023-02-08
Abstract: 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.
DOI: 10.1016/j.cell.2023.01.014
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00044-2