A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity

Adipic 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 in Saccharomyces cerevisiae to understand the cellular basis of adipic acid toxicity. Our screen revealed that KGD1 (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.