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 methyl (SM) was analyzed by DNA microarray technology. SM, a potent herbicide, inhibits acetolactate synthase, a branched-chain amino acid biosynthetic enzyme. Exposure of yeast cells to 0.2 microg/ml SM resulted in 40% growth inhibition, a Gcn4p-mediated induction of genes involved in amino acid and cofactor biosynthesis, and starvation response. The accumulation of intermediates led to the induction of stress response genes and the repression of genes involved in carbohydrate metabolism, nucleotide biosynthesis, and sulfur assimilation. Extended exposure to SM led to a relaxation of the initial response and induction of sugar transporter and ergosterol biosynthetic genes, as well as repression of histone and lipid metabolic genes. Exposure to 5 microg/ml SM resulted in >98% growth inhibition and stimulated a similar initial expression change, but with no relaxation after extended exposure. Instead, more stress response and DNA damage repair genes become induced, suggesting a serious cellular consequence. Other salient features of metabolic regulation, such as the coordinated expression of cofactor biosynthetic genes with amino acid biosynthetic ones, were evident from our data. A potential link between SM sensitivity and ergosterol metabolism was uncovered by expression profiling and confirmed by genetic analysis.
Jia
M H
MH
DuPont Central Research, DuPont Agricultural Biotechnology, Wilmington, Delaware 19880-0173, USA.
Larossa
R A
RA
Lee
J M
JM
Rafalski
A
A
Derose
E
E
Gonye
G
G
Xue
Z
Z
D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors; D000596:Amino Acids / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004875:Ergosterol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics* / Q000502:physiology; D006540:Herbicides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000596:Amino Acids; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006540:Herbicides; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D013453:Sulfonylurea Compounds; D000095:Acetolactate Synthase; D011494:Protein Kinases; C042031:sulfometuron methyl; D004875:Ergosterol