To explore network evolvability, we constructed recombinations of promoters (including regulatory regions) with different transcription or σ-factor genes in. Skip to main content. European Bioinformatics Institute. Evolvability and hierarchy in rewired bacterial gene networks. Sequencing DNA from several organisms has revealed that duplication and drift of existing genes have primarily moulded the contents of a given genome.

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Evolvability and hierarchy in rewired bacterial gene networks.

Significant enrichment was determined by comparing the set of transcription factor orthologs in question to the remaining transcription factors in the genome using a one tailed t -test assuming unequal variances. For example, accumulation of misfolded protein in cellular compartments can induce the unfolded protein response, leading to a reduction in cellular growth rate and protein production 8.

This suggests that suppression of enzyme and transport systems required for metabolism of unfavourable nitrogen sources improves heterologous production. Evolutionary dynamics of prokaryotic transcriptional regulatory networks. Abstract The ability to program cellular behaviour is a major goal of synthetic biology, with applications in health, agriculture and chemicals production. Conflict of interest statement.

Evolvability and hierarchy in rewired bacterial gene networks.

M Madan BabuSarah A. Pharmaceutical protein production by yeast: Flask culture was performed in ml Erlynmeyer flasks with 40 ml culture volumes in YPD and grown for 72 h. The clustering coefficient is a measure of how likely a node’s neighbours are to be connected with one another 41revealing how a node might facilitate localized information flow between its neighbors.

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Also, we noted that several rewiring solutions were isolated multiple times within a specific library, barring specific library biases, which we believe to be minimal considering the common amplicon origin of library components, this suggests that select rewiring solutions could improve expression of proteins with characteristic properties.

MAC1, isolated three times in the Insulin library a comparatively smaller simpler structured protein.

Systematic and synthetic approaches to rewire regulatory networks Jimin ParkHarris H. PloS one 6 6e This library-reporter vector was then linearized by restriction digestion using two separate enzymes to minimize library component loss due to double cutting and transformed into P.

Evolvability and hierarchy in rewired bacterial gene networks

The production of proteins and metabolites using engineered microbial strains is an area of significant interest for many industries, including therapeutics, biomass processing, food and beverage, agriculture and materials 1 — 5.

Related articles in Web of Science Google Scholar. They thus form a logical focus for further analysis. Proceedings of the National Academy of Sciences 4, We constructed a library consisting of promoters and CDSs that regulate cellular functions known to be important in protein overproduction, such as the unfolded protein response, heat shock response, carbon and nitrogen metabolism, and oxidative stress Figure 1C.

SNZ3 is a stationary phase induced protein involved in carbon source metabolism 2829This solution suggests that altered control of nitrogen regulation may also be important for lycopene production. URE2 also possesses glutathione-S-transferase activity which contributes to overcoming heavy metal and oxidant toxicity CoruzziAlejandro R.


URE2-like compared to control for growth normalized clones. For promoters D and E show clustering coefficient and hierarchy respectively. GIS2, a mRNA regulator has been shown to play a positive role in helping cells respond to stress induced during mitochondrial dysfunction and associates with stress granules in response to glucose deprivation 25 Primers were designed to amplify bp of selected promoters or the CDS of a gene.

We next asked if the CTA A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death.

Articles Cited by Co-authors. Topics Discussed in This Paper. A bistable gene switch for antibiotic biosynthesis: You must accept the terms and conditions. The improved enzymatic activity of the lipase further suggests that this rewiring solution is capable of producing functional protein. The network was analysed in Gephi http: This mean centered standardized data allowed us to compare gene expression across plates Figure 1D.

Proceedings of the National Academy of Sciences, Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. It is possible that rewiring network components with these properties reduce the distance regulatory information must travel to control network outputs.

Aravind Journal of molecular biology

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