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Optimization of fed-batch fermentation processes with bio-inspired algorithms
Rocha, Miguel; Mendes, Rui; Rocha, Orlando; Rocha, I.; Ferreira, E. C.The optimization of the feeding trajectories in fed-batch fermentation processes is a complex problem that has gained attention given its significant economical impact. A number of bio-inspired algorithms have approached this task with considerable success, but systematic and statistically significant comparisons of the different alternatives are still lacking. In this paper, the performance of different metahe...
Reconciling gene expression data with regulatory network models – a stimulon-ba...
Faria, José P.; Overbeek, Ross; Taylor, Ronald C.; Goelzer, Anne; Fromion, Vincent; Rocha, Miguel; Rocha, I.; Henry, Christopher S.The reconstruction of genome-scale metabolic models from genome annotations has become a routine practice in Systems Biology research. The potential of metabolic models for predictive biology is widely accepted by the scientific community, but these same models still lack the capability to account for the effect of gene regulation on metabolic activity. Our focus organism, Bacillus subtilis is most commonly fou...
Accuracy of prenatal culture in predicting intrapartum group B streptococcus co...
Florindo, C; Damião, V; Lima, J; Nogueira, I; Rocha, I; Caetano, P; Ribeiro, L; Viegas, S; Gomes, JP; Borrego, MJOBJECTIVE: To evaluate the positive predictive value (PPV) of group B Streptococcus (GBS) cultures at 35-37 weeks of gestation relative to GBS colonization status at delivery. METHODS: Rectovaginal swabs from 221 women at labor in four Lisbon hospitals were collected for GBS screening according to the CDC guidelines. RESULTS: The PPV was 24.4%. IAP was administered to 100% of prenatally GBS positive women. Ther...
Metabolic responses to recombinant bioprocesses in Escherichia coli
Carneiro, S.; Ferreira, E. C.; Rocha, I.Escherichia coli has been widely used for the production of recombinant proteins. However, the unbalances between host metabolism and recombinant biosynthesis continue to hamper the efficiency of these recombinant bioprocesses. The additional drainage of biosynthetic precursors toward recombinant processes burdens severely the metabolism of cells that, ultimately, elicits a series of stress responses, reducing ...
Identification of metabolic engineering targets through analysis of optimal and...
Soons, Zita; Ferreira, E. C.; Patil, Kiran Raosaheb; Rocha, I.Identification of optimal genetic manipulation strategies for redirecting substrate uptake towards a desired product is a challenging task owing to the complexity of metabolic networks, esp. in terms of large number of routes leading to the desired product. Algorithms that can exploit the whole range of optimal and suboptimal routes for product formation while respecting the biological objective of the cell are...
Towards a genome-scale metabolic model for the Kluyveromyces lactis yeast
Dias, O.; Gombert, Andreas Karoly; Ferreira, E. C.; Rocha, I.The interest in Kluyveromyces lactis (K. lactis) has begun in academia due to its ability to metabolize the betaglycoside (1). Since then, this yeast has been considered a model organism for studies in genetics and physiology (2). This yeast had its genome sequenced back in 2004 (3) and recently we have published a full metabolic re-annotation of its genome (4). This re-annotation can be used, among other appli...
iOD962 - the first genome-scale metabolic model of Kluyveromyces lactis
Dias, O.; Gombert, Andreas Karoly; Ferreira, E. C.; Rocha, I.The genome-scale metabolic model of Kluyveromyces lactis was reconstructed from its genome annotation. The result was the partially compartmentalized (5 compartments) iOD962 metabolic model composed of 2038 reactions and 1561 metabolites. Previous chemostate experiments were used to adjust the maintenance ATP parameter, and the model proved valuable when predicting the biomass, oxygen and carbon dioxide yields....
TNA4OptFlux : a software tool for the analysis of strain optimization strategies
Pinto, José P.; Pereira, Rui; Cardoso, João; Rocha, I.; Rocha, MiguelBACKGROUND:Rational approaches for Metabolic Engineering (ME) deal with the identification of modifications that improve the microbes' production capabilities of target compounds. One of the major challenges created by strain optimization algorithms used in these ME problems is the interpretation of the changes that lead to a given overproduction. Often, a single gene knockout induces changes in the fluxes of s...
Reconstruction of a genome-scale metabolic model for the filamentous fungus Ash...
Gomes, Daniel G.; Dias, O.; Ferreira, E. C.; Domingues, Lucília; Rocha, I.Metabolic models are an important tool for in silico simulation of cells’ behavior. Until now, a considerable number of metabolic models were released for several microorganisms. Ashbya gossypii is an industrially relevant fungus intensively used for riboflavin production with no model reported until now. Despite the high similarity with the Saccharomyces cerevisiae genome, A. gossypii contains only 4726 protei...
An integrated framework for strain optimization
Maia, Paulo; Rocha, I.; Rocha, MiguelThe identification of genetic modifications leading to mutant strains able to overproduce compounds of industrial interest is a challenging task in Metabolic Engineering (ME). Several methods have been proposed but, to some extent, none of them is suitable for all the specificities of each particular strain optimization problem. This work proposes an integrated framework that allows its users to configure and f...
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