Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism

Molecules

Robert St.Onge¹  Ulrich Schlecht¹  Curt Scharfe¹ 

[1] Department of Biochemistry, Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA;

关键词: yeast;    forward chemical genetics;    chemogenomic profiling;    glycolysis;    cancer metabolism;    Warburg effect;    mitochondria;    methotrexate;    leucovorin;   

DOI  :  10.3390/molecules171113098

来源: mdpi

【 摘 要 】

The many virtues that made the yeast Saccharomyces cerevisiae a dominant model organism for genetics and molecular biology, are now establishing its role in chemical genetics. Its experimental tractability (i.e., rapid doubling time, simple culture conditions) and the availability of powerful tools for drug-target identification, make yeast an ideal organism for high-throughput phenotypic screening. It may be especially applicable for the discovery of chemical probes targeting highly conserved cellular processes, such as metabolism and bioenergetics, because these probes would likely inhibit the same processes in higher eukaryotes (including man). Importantly, changes in normal cellular metabolism are associated with a variety of diseased states (including neurological disorders and cancer), and exploiting these changes for therapeutic purposes has accordingly gained considerable attention. Here, we review progress and challenges associated with forward chemical genetic screening in yeast. We also discuss evidence supporting these screens as a useful strategy for discovery of new chemical probes and new druggable targets related to cellular metabolism.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.