In this study, we used a yeast Alzheimer’s disease model in which amyloid-β peptides (Aβ42) accumulate and induce stress-related phenotypes similar to overexpression of recombinant proteins. We validated that suppressors of Aβ42 cytotoxicity could reduce cell stress and improve recombinant protein production. Omics analyses and reverse metabolic engineering reveal potential regulatory hubs in cellular metabolism and protein synthesis, which may provide guidelines for engineering other cell factories for efficient protein production.