scholarly journals Revisiting Demand Rules for Gene Regulation

2015 ◽  
Author(s):  
Mahendra K. Prajapat ◽  
Kirti Jain ◽  
Debika Choudhury ◽  
Gauri S. Choudhary ◽  
Supreet Saini
Keyword(s):  
Gene Regulation ◽  
Amino Acid ◽  
Amino Acid Biosynthesis ◽  
Stochastic Simulations ◽  
Carbon Utilization ◽  
Acid Biosynthesis ◽  
Natural Distribution ◽  
Transcription Network ◽  
E Coli ◽  
Micro Level

Starting with Savageau's pioneering work from 1970s, here, we choose the simplest transcription network and ask: How does the cell choose a regulatory topology from the different available possibilities? We study the natural distribution of topologies at genome, systems, and micro-level in E. coli and perform stochastic simulations to help explain the differences in natural distributions. Analyzing regulation of amino acid biosynthesis and carbon utilization in E. coli and B. subtilis, we observe many deviations from the demand rules, and observe an alternate pattern emerging. Overall, our results indicate that choice of topology is drawn randomly from a pool of all networks which satisfy the kinetic requirements of the cell, as dictated by physiology. In short, simply, the cell picks "whatever works".

scholarly journals Comparison of ΔrelA Strains of Escherichia coli and Salmonella enterica Serovar Typhimurium Suggests a Role for ppGpp in Attenuation Regulation of Branched-Chain Amino Acid Biosynthesis

2001 ◽  
Vol 183 (21) ◽  
pp. 6184-6196 ◽  
Author(s):  
K. Tedin ◽  
F. Norel
Keyword(s):  
Amino Acid ◽  
Amino Acid Biosynthesis ◽  
Chain Elongation ◽  
Acid Biosynthesis ◽  
E Coli ◽  
Growth Recovery ◽  
Branched Chain Amino Acid ◽  
Serovar Typhimurium ◽  
Branched Chain ◽  
K 12

ABSTRACT The growth recovery of Escherichia coli K-12 andSalmonella enterica serovar Typhimurium ΔrelAmutants were compared after nutritional downshifts requiring derepression of the branched-chain amino acid pathways. Because wild-type E. coli K-12 and S. enterica serovar Typhimurium LT2 strains are defective in the expression of the genes encoding the branch point acetohydroxy acid synthetase II (ilvGM) and III (ilvIH) isozymes, respectively, ΔrelA derivatives corrected for these mutations were also examined. Results indicate that reduced expression of the known global regulatory factors involved in branched-chain amino acid biosynthesis cannot completely explain the observed growth recovery defects of the ΔrelA strains. In the E. coli K-12 MG1655 ΔrelA background, correction of the preexisting rph-1 allele which causes pyrimidine limitations resulted in complete loss of growth recovery. S. enterica serovar Typhimurium LT2 ΔrelA strains were fully complemented by elevated basal ppGpp levels in an S. enterica serovar Typhimurium LT2 ΔrelA spoT1 mutant or in a strain harboring an RNA polymerase mutation conferring a reduced RNA chain elongation rate. The results are best explained by a dependence on the basal levels of ppGpp, which are determined byrelA-dependent changes in tRNA synthesis resulting from amino acid starvations. Expression of the branched-chain amino acid operons is suggested to require changes in the RNA chain elongation rate of the RNA polymerase, which can be achieved either by elevation of the basal ppGpp levels or, in the case of the E. coli K-12 MG1655 strain, through pyrimidine limitations which partially compensate for reduced ppGpp levels. Roles for ppGpp in branched-chain amino acid biosynthesis are discussed in terms of effects on the synthesis of known global regulatory proteins and current models for the control of global RNA synthesis by ppGpp.

scholarly journals Allosteric Feedback Inhibition Enables Robust Amino Acid Biosynthesis in E. coli by Enforcing Enzyme Overabundance

Cell Systems ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 66-75.e8 ◽  
Author(s):  
Timur Sander ◽  
Niklas Farke ◽  
Christoph Diehl ◽  
Michelle Kuntz ◽  
Timo Glatter ◽  
...  
Keyword(s):  
Amino Acid ◽  
Feedback Inhibition ◽  
Amino Acid Biosynthesis ◽  
Acid Biosynthesis ◽  
E Coli

scholarly journals Homocysteine Toxicity in Escherichia coli Is Caused by a Perturbation of Branched-Chain Amino Acid Biosynthesis

2005 ◽  
Vol 187 (13) ◽  
pp. 4362-4371 ◽  
Author(s):  
Nina L. Tuite ◽  
Katy R. Fraser ◽  
Conor P. O'Byrne
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Biosynthetic Pathway ◽  
Amino Acid Biosynthesis ◽  
Inhibitory Effects ◽  
Acid Biosynthesis ◽  
Threonine Deaminase ◽  
E Coli ◽  
Branched Chain Amino Acid ◽  
Branched Chain

ABSTRACT In Escherichia coli the sulfur-containing amino acid homocysteine (Hcy) is the last intermediate on the methionine biosynthetic pathway. Supplementation of a glucose-based minimal medium with Hcy at concentrations greater than 0.2 mM causes the growth of E. coli Frag1 to be inhibited. Supplementation of Hcy-treated cultures with combinations of branched-chain amino acids containing isoleucine or with isoleucine alone reversed the inhibitory effects of Hcy on growth. The last intermediate of the isoleucine biosynthetic pathway, α-keto-β-methylvalerate, could also alleviate the growth inhibition caused by Hcy. Analysis of amino acid pools in Hcy-treated cells revealed that alanine, valine, and glutamate levels are depleted. Isoleucine could reverse the effects of Hcy on the cytoplasmic pools of valine and alanine. Supplementation of the culture medium with alanine gave partial relief from the inhibitory effects of Hcy. Enzyme assays revealed that the first step of the isoleucine biosynthetic pathway, catalyzed by threonine deaminase, was sensitive to inhibition by Hcy. The gene encoding threonine deaminase, ilvA, was found to be transcribed at higher levels in the presence of Hcy. Overexpression of the ilvA gene from a plasmid could overcome Hcy-mediated growth inhibition. Together, these data indicate that in E. coli Hcy toxicity is caused by a perturbation of branched-chain amino acid biosynthesis that is caused, at least in part, by the inhibition of threonine deaminase.

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