Exceptional solvent tolerance in Yarrowia lipolytica is enhanced by sterols

Green organic solvents such as ionic liquids (ILs) have versatile use but are inhibitory to microbes even at low concentrations of 0.5–1.0% (v/v) ILs. We discovered the oleaginous yeast Yarrowia lipolytica can grow in 10% (v/v) of 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), which makes it more tolerant than most engineered microorganisms and naturally screened isolates. However, the underlying mechanism of IL tolerance in Y. lipolytica is not understood. Through adaptive laboratory evolution, in combination with physiological characterization and omics analysis, we shed light on the underlying mechanism of how Y. lipolytica restructures its membrane to tolerate different types of ILs at high levels up to 18% ILs. Specifically, we discovered that sterols play a key role for exceptional IL tolerance in Y. lipolytica.