Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

摘要: Gene dosage toxicity (GDT) is an important factor that determines optimal levels of protein abundances, yet its molecular underpinnings remain unknown. Here, we demonstrate overexpression DHFR in E. coli causes a toxic metabolic imbalance triggered by interactions with several functionally related enzymes. Though deleterious the regime, surprisingly, these are beneficial at physiological concentrations, implying their functional significance vivo. Moreover, found orthologous proteins had minimal effect on all cellular organization - molecular, systems, and phenotypic, sharp contrast to DHFR. Dramatic difference GDT between 'E. coli's self' 'foreign' suggests crucial role evolutionary selection shaping protein-protein interaction (PPI) networks whole proteome level. This study shows how perturbs dynamic metabolon weak potentially PPI, consequences for state cells fitness.