By analyzing the genetic diversity of undomesticated Y. lipolytica strains, coupled with detailed strain characterization and proteomic analysis, Associate Professor Cong Trinh’s team revealed metabolic processes and regulatory elements conferring desirable phenotypes for growth, sugar utilization, and lipid accumulation in undetoxified biomass hydrolysates by these natural variants. This study provides a better understanding of the robust metabolism of Y. lipolytica and suggests potential metabolic engineering strategies to enhance its performance. This research is published in mSystems and funded by the DOE Office of Science’s Biological and Environmental Research (BER) program (DE-SC0019412).