Amity Institute of Biotechnology, Amity University Haryana, Gurugram, India.
Amity Institute of Integrative Sciences and Health, Amity University Haryana, Gurugram, India.
mBio. 2022 Jun 28;13(3):e0095522. doi: 10.1128/mbio.00955-22. Epub 2022 Apr 25.
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 -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.
多年来，人们一直强调开发高通量平台，以帮助识别药物和外源性化合物的转运蛋白。然而，这些方法的主要障碍包括底物的混杂性和膜转运蛋白的功能冗余。为了解决这些问题，Almeida 及其同事（L. D. Almeida、A. S. F. Silva、D. C. Mota、A. A. Vasconcelos 等人，mBio 12(6):e03221-21, 2021）巧妙地利用了酵母遗传学的力量，为 122 种非必需的质膜转运蛋白创建了一个双基因缺失文库，这使得高通量鉴定药物/外源性化合物转运蛋白变得更加容易。在研究细胞毒性化合物文库时，作者发现唑类化合物的化学结构与可能的进出口途径之间存在很强的相关性。有趣的是，作者还发现肌醇转运蛋白 Itr1 负责三唑和咪唑抗真菌化合物的摄取，并提出 ABC 转运蛋白 Pdr5 可能参与了苯并咪唑类农药的摄取。
