Reference: Krappmann S, et al. (2000) Coevolution of transcriptional and allosteric regulation at the chorismate metabolic branch point of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 97(25):13585-90

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Abstract


Control of transcription and enzyme activities are two interwoven regulatory systems essential for the function of a metabolic node. Saccharomyces cerevisiae strains differing in enzyme activities at the chorismate branch point of aromatic amino acid biosynthesis were constructed by recombinant DNA technology. Expression of an allosterically unregulated, constitutively activated chorismate mutase encoded by the ARO7(T226I) (ARO7(c)) allele depleted the chorismate pool. The resulting tryptophan limitation caused growth defects, which could be counteracted only by transcriptional induction of TRP2 encoding the competing enzyme anthranilate synthase. ARO7 expression is not transcriptionally regulated by amino acids. Transcriptional activation of the ARO7(c) allele led to stronger growth retardation upon tryptophan limitation. The same effect was achieved by removing the competing enzyme anthranilate synthase, which is encoded by the TRP2 gene, from the transcriptional control. The allelic situation of ARO7(c) being under general control instead of TRP2 resulted in severe growth defects when cells were starved for tryptophan. In conclusion, the specific regulatory pattern acting on enzymatic activities at the first metabolic node of aromatic amino acid biosynthesis is necessary to maintain proper flux distribution. Therefore, the evolution of the sophisticated allosteric regulation of yeast chorismate mutase requires as prerequisite (i) that the encoding ARO7 gene is not transcriptionally regulated, whereas (ii) the transcription of the competing feedback-regulated anthranilate synthase-encoding gene is controlled by availability of amino acids.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Krappmann S, Lipscomb WN, Braus GH
Primary Lit For
TRP2 | GCN4 | ARO7 | Anthranilate synthase complex

Phenotype Annotations 1 entry for 1 gene


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GenePhenotypeExperiment TypeMutant InformationStrain BackgroundChemicalDetails
ARO7vegetative growth: decreased rate
classical geneticsactivation
Allele: aro7-T226I

T226I; constitutively active with 10-fold increased basal activity; unresponsive to activation by tryptophan or inhibition by tyrosine

S288C0.0001 M 5-methyltryptophanMedia: Trp starvation
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