DoesEscherichia coliOptimize the Economics of the translation Process?

Solomovici, Jean; Lesnik, Thierry; Reiss, Claude

doi:10.1006/jtbi.1996.0310

Cited by 32 publications

(27 citation statements)

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“…To explore the effect of slower translation of HlyA, we used a stochastic mathematical model of translation to determine which codons could be changed to significantly decrease the translation rate without altering the amino acid sequence. We defined rare codons as those whose corresponding tRNA is less that 1% of the total tRNA (as tabulated in Solomovici et al, 1997). Through simulation, we explored substitutions in a small number of adjacent codons in the hlyA sequence that would produce the largest number of rare codons without altering the amino acid sequence.…”

Section: Recovery Of the Hypersecretion Phenotype In A Known Systemmentioning

confidence: 99%

“…The ''slow'' sequence contained a total of eight rare codons, and was made by altering the sequence as shown in Figure 3. Using tRNA abundance tables (Solomovici et al, 1997), the mathematical model predicted that the rate of translation of the ''slow'' hlyA sequence was 37% lower than that of the original sequence. A comparable simulation based on frequency of codon usage (tabulated in Kanehisa, 2002) separately predicted a 39% decrease in translation rate.…”

Section: Recovery Of the Hypersecretion Phenotype In A Known Systemmentioning

confidence: 99%

“…The use of rare codons in a gene has been shown to reduce its rate of translation, because the number of available aminoacyltRNAs is limited (Solomovici et al, 1997). To explore the effect of slower translation of HlyA, we used a stochastic mathematical model of translation to determine which codons could be changed to significantly decrease the translation rate without altering the amino acid sequence.…”

Section: Recovery Of the Hypersecretion Phenotype In A Known Systemmentioning

confidence: 99%

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Engineering HlyA hypersecretion inEscherichia coli based on proteomic and microarray analyses

Lee

2004

Biotechnol. Bioeng.

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Escherichia coli is a common host for recombinant protein production for biotechnology applications. Secretion to the extracellular media has the potential to reduce protein aggregation and to simplify downstream purification. However, the complexity of the mechanisms of protein secretion has confounded prior attempts to engineer enhanced secretion phenotypes. Here, mutagenesis was used to perturb E. coli W3110 cells secreting HlyA via a Type I pathway. An activity assay identified a mutant secreting fourfold more active alpha-hemolysin than the parent strain. The mutant was characterized using both high-density microarrays for mRNA profiling and a proteomics strategy for protein expression. The relative mRNA and protein expression levels of tRNA-synthetases were decreased in the mutant compared to the parent. A mathematical model of prokaryotic translation was used to design a variant of the hlyA gene that encodes the same amino acid sequence but uses rare codons to slow the rate of translation by altering five bases. Analysis of the parent strain transformed with a plasmid containing this variant gene resulted in the recovery of, and further improvement upon, the selected hypersecretion phenotype. These results present one of the first successful metabolic engineering attempts based on molecular information provided by mRNA and protein expression profiling approaches and resulting in a phenotype useful to the biotechnology community.

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Section: Recovery Of the Hypersecretion Phenotype In A Known Systemmentioning

confidence: 99%

Section: Recovery Of the Hypersecretion Phenotype In A Known Systemmentioning

confidence: 99%

Section: Recovery Of the Hypersecretion Phenotype In A Known Systemmentioning

confidence: 99%

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Engineering HlyA hypersecretion inEscherichia coli based on proteomic and microarray analyses

Lee

2004

Biotechnol. Bioeng.

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“…Elongation rates at each codon were estimated using commonly accepted values for the availability of tRNA in E. coli [45]. The rate at each codon was assumed proportional (with an arbitrary proportionality constant) to the availability of the tRNA decoding that codon, as in [48].…”

Section: Simulation Of a Real Gene Sequencementioning

confidence: 99%

Totally asymmetric exclusion process with extended objects: A model for protein synthesis

2003

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The process of protein synthesis in biological systems resembles a one dimensional driven lattice gas in which the particles have spatial extent, covering more than one lattice site. We expand the well studied Totally Asymmetric Exclusion Process (TASEP), in which particles typically cover a single lattice site, to include cases with extended objects. Exact solutions can be determined for a uniform closed system. We analyze the uniform open system through two approaches. First, a continuum limit produces a modified diffusion equation for particle density profiles. Second, an extremal principle based on domain wall theory accurately predicts the phase diagram and currents in each phase. Finally, we briefly consider approximate approaches to a non-uniform open system with quenched disorder in the particle hopping rates and compare these approaches with Monte Carlo simulations.

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“…Scenarios 1–4 are increasingly complex, and represent deliberate attempts to assign translation rates to the unmeasured codons in a way that increases s bias while remaining consistent with patterns found in the empirical data. Furthermore, in Scenario 5, we apply a theoretical approach [62] for predicting optimal codon-specific translation rates that does not rely on empirical translation rate measurements at all, but only on codon frequency and tRNA abundance data.…”

Section: Resultsmentioning

confidence: 99%

Differences in codon bias cannot explain differences in translational power among microbes

Dethlefsen

Schmidt

2005

BMC Bioinformatics

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Background: Translational power is the cellular rate of protein synthesis normalized to the biomass invested in translational machinery. Published data suggest a previously unrecognized pattern: translational power is higher among rapidly growing microbes, and lower among slowly growing microbes. One factor known to affect translational power is biased use of synonymous codons. The correlation within an organism between expression level and degree of codon bias among genes of Escherichia coli and other bacteria capable of rapid growth is commonly attributed to selection for high translational power. Conversely, the absence of such a correlation in some slowly growing microbes has been interpreted as the absence of selection for translational power. Because codon bias caused by translational selection varies between rapidly growing and slowly growing microbes, we investigated whether observed differences in translational power among microbes could be explained entirely by differences in the degree of codon bias. Although the data are not available to estimate the effect of codon bias in other species, we developed an empiricallybased mathematical model to compare the translation rate of E. coli to the translation rate of a hypothetical strain which differs from E. coli only by lacking codon bias.

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DoesEscherichia coliOptimize the Economics of the translation Process?

Cited by 32 publications

References 0 publications

Engineering HlyA hypersecretion inEscherichia coli based on proteomic and microarray analyses

Engineering HlyA hypersecretion inEscherichia coli based on proteomic and microarray analyses

Totally asymmetric exclusion process with extended objects: A model for protein synthesis

Differences in codon bias cannot explain differences in translational power among microbes

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