User:Josh K. Michener/Feedback/TechTalk
"To effect facile manipulation of gene expression across a full continuum of possible expression levels, we recently created a library of mutant promoters. Here, we provide the detailed characterization of our yeast promoter collection comprising 11 mutants of the strong constitutive Saccharomyces cerevisiae TEF1 promoter. The activities of the mutant promoters range between about 8% and 120% of the activity of the unmutated TEF1 promoter."
"The basic idea of our paper is that time dependent gene expression enables cells to adapt their metabolic capabilities in an optimal way to varying external conditions."
"It has been proposed, but not demonstrated, that autoregulatory, negative feedback loops in gene circuits provide stability, thereby limiting the range over which the concentrations of network components fluctuate. Here we have designed and constructed simple gene circuits consisting of a regulator and transcriptional repressor modules in Escherichia coli and we show the gain of stability produced by negative feedback."
"Negative autoregulation shifts noise to higher frequencies where it is more easily filtered out by gene networks"
"We compare two strategies of gene regulation: a simple transcription unit and a negative autoregulatory circuit. The two circuits can be designed to reach the same steady-state level of protein concentration, by having differing values for the maximal production rate of their promoters. We will show that the negative autoregulatory circuit approaches its steady-state value much faster than the non-autoregulatory circuit."
"We identified two design principles: the closer the enzyme is to the beginning of the pathway, the shorter the response time of the activation of its promoter and the higher its maximal promoter activity. Mathematical analysis suggests that this 'just-in-time' transcription program is optimal under constraints of rapidly reaching a production goal with minimal total enzyme production." 
"Perhaps the major function of this system is to partition potentially damaging processes from sensitive biosynthetic events, where bursts of pro- and anti-oxidants are produced out-of-phase every cycle."
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- Klipp E, Heinrich R, and Holzhütter HG. Prediction of temporal gene expression. Metabolic opimization by re-distribution of enzyme activities. Eur J Biochem. 2002 Nov;269(22):5406-13.
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- Austin DW, Allen MS, McCollum JM, Dar RD, Wilgus JR, Sayler GS, Samatova NF, Cox CD, and Simpson ML. Gene network shaping of inherent noise spectra. Nature. 2006 Feb 2;439(7076):608-11. DOI:10.1038/nature04194 |
- Rosenfeld N, Elowitz MB, and Alon U. Negative autoregulation speeds the response times of transcription networks. J Mol Biol. 2002 Nov 8;323(5):785-93.
- Zaslaver A, Mayo AE, Rosenberg R, Bashkin P, Sberro H, Tsalyuk M, Surette MG, and Alon U. Just-in-time transcription program in metabolic pathways. Nat Genet. 2004 May;36(5):486-91. DOI:10.1038/ng1348 |
- Lloyd D and Murray DB. The temporal architecture of eukaryotic growth. FEBS Lett. 2006 May 22;580(12):2830-5. DOI:10.1016/j.febslet.2006.02.066 |
- Alper H, Fischer C, Nevoigt E, and Stephanopoulos G. Tuning genetic control through promoter engineering. Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12678-83. DOI:10.1073/pnas.0504604102 |
- Lee SK and Keasling JD. A propionate-inducible expression system for enteric bacteria. Appl Environ Microbiol. 2005 Nov;71(11):6856-62. DOI:10.1128/AEM.71.11.6856-6862.2005 |