A Biochemical Genomics Approach for Identifying Genes by the Activity of Their Products

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Abstract
For the identification of yeast genes specifying biochemical activities, a genomic strategy that is rapid, sensitive, and widely applicable was developed with an array of 6144 individual yeast strains, each containing a different yeast open reading frame (ORF) fused to glutathione S-transferase (GST). For the identification of ORF-associated activities, strains were grown in defined pools, and GST-ORFs were purified. Then, pools were assayed for activities, and active pools were deconvoluted to identify the source strains. Three previously unknown ORF-associated activities were identified with this strategy: a cyclic phosphodiesterase that acts on adenosine diphosphate–ribose 1"-2" cyclic phosphate (Appr>p), an Appr-1"-p–processing activity, and a cytochrome c methyltransferase.