Genetic chemistry: production of non-native compounds in yeast

Abstract

The tools and perspectives that chemists bring to the study of biological systems have yielded very important discoveries and opened many new research possibilities over the years (Hopkins AL: Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 2008, 11:682-690; Lehar J, Stockwell BR, Giaever G, Nislow C: Combination chemical genetics. Nat Chem Biol 2008, 11:674-681. This work describes use of genome level data to discover and understand higher order pleiotropic effects of combinations of drugs). Chemical biology has an ever-growing toolbox that has been expanding its reach into many different aspects of the study and utilization of biological systems (Strombergsson H, Kleywegt G: A chemogenomic view on protein-ligand spaces. BMC Bioinformatics 2009, 10(Suppl 6):S13; Bumpus BB, Evens BS, Thomas PM, Ntai I, Kelleher NI: A proteomics approach to discovering natural products and their biosynthetic pathways. Nat Biotechnol 2009, 27:951-956. This reviews techniques that allow for the identification of biochemical pathways that produce molecules of interest under very specific situations; Altamn KH, Buchner J, Kessler H, Diederich F, Krautler B, Lippard S, Liskamp R, Muller K, Nolan EM, Samori B, et al.: The state of the art of chemical biology. Chembiochem 2009, 10:16-29) including the study and utilization of biological systems in yeast. This review will describe recent successes in the use of yeast for both discovery and production of non-native secondary metabolites focused on pharmaceutically relevant compounds.