The Saccharomyces cerevisiae methyltransferase encoded by TMT1 catalyzes the AdoMet-dependent monomethylation of 3-isopropylmalate, an intermediate of the leucine biosynthetic pathway. The biological significance of methylating 3-isopropylmalate and the relationship between Tmt1 and the leucine biosynthetic pathway is not yet established. We present evidence here showing that methylation of 3-isopropylmalate functions to extracellularly signal yeast to grow invasively. We show that methyl esterification generates 3-isopropylmalate-1-methyl ester. We find that the Tmt1 methyltransferase functions independently of the biosynthetic pathway but is induced when cells are starved for amino acids; the largest induction is observed with the removal of leucine from the media. This amino acid starvation stress response is controlled by the transcriptional activator Gcn4. After methylation, 3-isopropylmalate methyl ester is secreted into the media within 3 h. Thin layer chromatography and gas chromatography mass spectroscopy confirm that the intact molecule is secreted. Finally, we show that purified 3-isopropylmalate methyl ester can enhance the ability of the haploid yeast strain 10560-23C to grow invasively. Our data identifies 3-isopropylmalate methyl ester as an autoinductive molecule that provides a signal to yeast to switch from vegetative to invasive growth in response to amino acid starvation.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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