A Chemogenomic Toolkit to Evaluate the “Ins and Outs” of Yeast Plasma Membrane Transporters

Abstract

Over the years, there has been a lot of emphasis on the development of high-throughput platforms that help identify transporters of drugs and xenobiotics. However, major hinderances in these approaches include substrate promiscuity and functional redundancy of membrane transporters. To tackle such issues, Almeida and colleagues (L. D. Almeida, A. S. F. Silva, D. C. Mota, A. A. Vasconcelos, et al., mBio 12 (6):e03221-21, 2021) elegantly used the power of yeast genetics and created a double gene deletion library for 122 nonessential plasma membrane transporters that facilitates high-throughput identification of drug/xenobiotic transporters. While examining a library of cytotoxic compounds, the authors identified a strong correlation between the chemical structure of azoles and possible import/export routes. Interestingly, the authors also identified the myo-inositol transporter Itr1 to be responsible for import of triazole and imidazole antifungal compounds and proposed a role for the ABC transporter Pdr5 in carbendazim uptake.