(140b) Modulation of Membrane Lipid Parameters Enabled Prediction of Cell Growth in Combined Inhibitory Conditions

Robust biocatalysts support bio-production at industrially relevant titers. Engineering of the microbial cell membrane engineering to increase microbial robustness has shown promising outcomes. Characterization of the effects of representative inhibitors on the cell membrane can contribute to rational design strategies. In this study, we engineered E. coli strains for a range of membrane lipid metrics and properties when the cells were cultured in several distinct inhibitory conditions. We used experimental data from single culture conditions to identify correlations between membrane composition metrics, membrane physical properties, and growth of the strain. This information for distinct inhibitors was used to estimate trends for culture conditions with multiple inhibitors. We experimentally validated the response to inhibitors to various levels by combining 2% v/v ethanol, 2.5 mM furfural, and 42 ºC in minimal media. Membrane hydrophobicity in the combined condition was found to be a meaningful feature that enabled the prediction of cell growth in the combined condition relative to estimations based on the growth rates from individual conditions. This work demonstrates that the modulation of membrane features, specifically the lipid composition, can be utilized to engineer microbial robustness for inhibitory conditions.