Phase separation of the PRPP amidotransferase into dynamic condensates promotes de novo purine synthesis in yeast.

ABSTRACT: De novo purine synthesis (DPS) is up-regulated under conditions of high purine demand to ensure the production of genetic materials and chemical energy, thereby supporting cell proliferation. However, the regulatory mechanisms governing DPS remain unclear. We herein show that PRPP amidotransferase (PPAT), the rate-limiting enzyme in DPS, forms dynamic and motile condensates in Saccharomyces cerevisiae cells under a purine-depleted environment. The formation and maintenance of condensates requires phase separation, which is driven by target of rapamycin complex 1 (TORC1)-induced ribosome biosynthesis. The self-assembly of PPAT molecules facilitates condensate formation, with intracellular PRPP and purine nucleotides both regulating this self-assembly. Moreover, molecular dynamics simulation

SUBMITTER: Takaine M 

PROVIDER: S-EPMC12017579 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature