摘要：SummaryAdipic acid production by yeast fermentation is gaining attention as a renewable source of platform chemicals for making nylon products. However, adipic acid toxicity inhibits yeast growth and fermentation. Here, we performed a chemogenomic screen inSaccharomyces cerevisiaeto understand the cellular basis of adipic acid toxicity. Our screen revealed thatKGD1(a key gene in the tricarboxylic acid cycle) deletion improved tolerance to adipic acid and its toxic precursor, catechol. Conversely, disrupting ergosterol biosynthesis as well as protein trafficking and vacuolar transport resulted in adipic acid hypersensitivity. Notably, we show that adipic acid disrupts the Membrane Compartment of Can1 (MCC) on the plasma membrane and impacts endocytosis. This was evidenced by the rapid internalization of Can1 for vacuolar degradation. As ergosterol is an essential component of the MCC and protein trafficking mechanisms are required for endocytosis, we highlight the importance of these cellular processes in modulating adipic acid toxicity.Graphical abstractDisplay OmittedHighlights•Deletion of the TCA cycle geneKGD1improves tolerance to adipic acid and catechol•Ergosterol and Pdr12 play non-overlapping roles protecting cell from adipic acid•Adipic acid-induced plasma membrane localization of Pdr12 is independent of ergosterol•Adipic acid disrupts the Membrane Compartment of Can1 (MCC) and induces endocytosisCell Biology; Systems Biology
