Laboratory evolutions lead to reproducible mutations in PDR3 conferring resistance to MCHM

The solubility of protein complexes and membraneless compartments is maintained by liquid-liquid phase separation (LLPS). Phase transition is induced or dissolved by biological hydrotropes such asATP and RNA. 4-methylcyclohexane methanol (MCHM), an alicyclic alcohol, is a synthetic hydrotropethat induces a starvation response by upregulation of biosynthetic pathways despite the availability ofnutrients. To investigate how cellular metabolism can tolerate changes in LLPS, we evolved eightMHCM-resistant strains of S. cerevisiae.