Department of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Japan.
Department of Applied Biological Chemistry, Graduate School of Agriculture, Osaka Metropolitan University, Sakai, Japan.
PLoS One. 2023 Apr 13;18(4):e0283002. doi: 10.1371/journal.pone.0283002. eCollection 2023.
Spatial reorganization of metabolic enzymes to form the "metabolic enzymes transiently assembling (META) body" is increasingly recognized as a mechanism contributing to regulation of cellular metabolism in response to environmental changes. A number of META body-forming enzymes, including enolase (Eno2p) and phosphofructokinase, have been shown to contain condensate-forming regions. However, whether all META body-forming enzymes have condensate-forming regions or whether enzymes have multiple condensate-forming regions remains unknown. The condensate-forming regions of META body-forming enzymes have potential utility in the creation of artificial intracellular enzyme assemblies. In the present study, the whole sequence of yeast pyruvate kinase (Cdc19p) was searched for condensate-forming regions. Four peptide fragments comprising 27-42 amino acids were found to form condensates. Together with the fragment previously identified from Eno2p, these peptide regions were collectively termed "META body-forming sequences (METAfos)." METAfos-tagged yeast alcohol dehydrogenase (Adh1p) was found to co-localize with META bodies formed by endogenous Cdc19p under hypoxic conditions. The effect of Adh1p co-localization with META bodies on cell metabolism was further evaluated. Expression of Adh1p fused with a METAfos-tag increased production of ethanol compared to acetic acid, indicating that spatial reorganization of metabolic enzymes affects cell metabolism. These results contribute to understanding of the mechanisms and biological roles of META body formation.
代谢酶的空间重排形成“代谢酶瞬时组装(META)体”,这一机制越来越被认为是细胞代谢对环境变化作出响应的一种调控机制。许多形成 META 体的酶,包括烯醇化酶(Eno2p)和磷酸果糖激酶,已被证明含有凝聚物形成区域。然而,是否所有形成 META 体的酶都具有凝聚物形成区域,或者酶是否具有多个凝聚物形成区域,目前尚不清楚。形成 META 体的酶的凝聚物形成区域在创建人工细胞内酶组装方面具有潜在的应用价值。在本研究中,搜索了酵母丙酮酸激酶(Cdc19p)的整个序列,以寻找凝聚物形成区域。发现了四个包含 27-42 个氨基酸的肽片段可形成凝聚物。与先前从 Eno2p 中鉴定出的片段一起,这些肽区域被统称为“META 体形成序列(METAfos)”。在缺氧条件下,METAfos 标记的酵母醇脱氢酶(Adh1p)与内源性 Cdc19p 形成的 META 体共定位。进一步评估了 Adh1p 与 META 体共定位对细胞代谢的影响。与融合了 METAfos 标签的 Adh1p 相比,表达 Adh1p 增加了乙醇的产量,而减少了乙酸的产量,这表明代谢酶的空间重排影响了细胞代谢。这些结果有助于理解 META 体形成的机制和生物学作用。