Global expression profiling of yeast treated with an inhibitor of amino acid biosynthesis, sulfometuron methyl

The expression pattern of 1,529 yeast genes in response to sulfometuron met hyl (SM) was analyzed by DNA microarray technology. SM, a potent herbicide, inhibits acetolactate synthase, a branched-chain amino acid biosynthetic e nzyme. Exposure of yeast cells to 0.2 mu g/ml SM resulted in 40% growth inh ibition, a Gcn4p-mediated induction of genes involved in amino acid and cof actor biosynthesis, and starvation response. The accumulation of intermedia tes led to the induction of stress response genes and the repression of gen es involved in carbohydrate metabolism, nucleotide biosynthesis, and sulfur assimilation. Extended exposure to SM led to a relaxation of the initial r esponse and induction of sugar transporter and ergosterol biosynthetic gene s, as well as repression of histone and lipid metabolic genes. Exposure to 5 mu g/ml SM resulted in >98% growth inhibition and stimulated a similar in itial expression change, but with no relaxation after extended exposure. In stead, more stress response and DNA damage repair genes become induced, sug gesting a serious cellular consequence. Other salient features of metabolic regulation, such as the coordinated expression of cofactor biosynthetic ge nes with amino acid biosynthetic ones, were evident from our data. A potent ial link between SM sensitivity and ergosterol metabolism was uncovered by expression profiling and confirmed by genetic analysis.