In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 25 ( 2000-12-05), p. 13585-13590
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.240469697
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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