Biology subjects

Ferreira, E. C.

Publications and source records attributed to Ferreira, E. C..

3 recordsLinked to original sources

bioRxiv2021

BioISO: an objective-oriented application for assisting the curation of genome-scale metabolic models

As the reconstruction of Genome-Scale Metabolic Models becomes standard practice in systems biology, the number of organisms having at least one metabolic model at the genome-scale is peaking at an unprecedented scale. The automation of several laborious tasks, such as gap-finding and gap-filling, allowed to develop GSMMs for poorly described organisms. However, such models quality can be compromised by the automation of several steps, which may lead to erroneous phenotype simulations. The Biological networks constraint-based In Silico Optimization (BioISO) is a computational tool aimed at accelerating the reconstruction of Genome-Scale Metabolic Models. This tool facilitates the manual curation steps by reducing the large search spaces often met when debugging in silico biological models. BioISO uses a recursive relation-like algorithm and Flux Balance Analysis to evaluate and guide debugging of in silico phenotype simulations. The potential of BioISO to guide the debugging of model reconstructions was showcased using GSMMs available in literature and compared with the results of two other state-of-the-art gap-filling tools (Meneco and fastGapFill). Furthermore, BioISO was used as Menecos gap-finding algorithm to reduce the number of proposed solutions (reaction sets) for filling the gaps. BioISO was implemented as a webserver available at https://bioiso.bio.di.uminho.pt; and integrated into merlin as a plugin. BioISOs implementation as a Python package can also be retrieved from https://github.com/BioSystemsUM/BioISO.

systems biology↗

bioRxiv2021

merlin v4.0: an updated platform for the reconstruction of high-quality genome-scale metabolic models

Genome-scale metabolic models have been recognised as useful tools for better understanding living organisms metabolism. merlin (https://www.merlin-sysbio.org/) is an open-source and user-friendly resource that hastens the models reconstruction process, conjugating manual and automatic procedures, while leveraging the users expertise with a curation-oriented graphical interface. An updated and redesigned version of merlin is herein presented. Since 2015, several features have been implemented in merlin, along with deep changes in the software architecture, operational flow, and graphical interface. The current version (4.0) includes the implementation of novel algorithms and third-party tools for genome functional annotation, draft assembly, model refinement, and curation. Such updates increased the user base, resulting in multiple published works, including genome metabolic (re-)annotations and model reconstructions of multiple (lower and higher) eukaryotes and prokaryotes. merlin version 4.0 is the only tool able to perform template based and non-template based draft reconstructions, while achieving competitive performance compared to state-of-the art tools both for well and less-studied organisms.

bioinformatics↗

bioRxiv2020

A kinetic model of the central carbon metabolism for acrylic acid production in Escherichia coil

Acrylic acid is a value-added chemical used in industry to produce diapers, coatings, paints, and adhesives, among many others. Due to its economic importance, there is currently a need for new and sustainable ways to synthesise it. Recently, the focus has been laid in the use of Escherichia coli to express the full bio-based pathway using 3-hydroxypropionate as an intermediary through three distinct pathways (glycerol, malonyl-CoA, and {beta}-alanine). Hence, the goals of this work were to use COPASI software to assess which of the three pathways has a higher potential for industrial-scale production, from either glucose or glycerol, and identify potential targets to improve the biosynthetic pathways yields. When compared to the available literature, the models developed during this work successfully predict the production of 3-hydroxypropionate, using glycerol as carbon source in the glycerol pathway, and using glucose as a carbon source in the malonyl-CoA and {beta}-alanine pathways. Finally, this work allowed to identify four potential over-expression targets (glycerol-3-phosphate dehydrogenase (G3pD), acetyl-CoA carboxylase (AccC), aspartate aminotransferase (AspAT), and aspartate carboxylase (AspC)) that should, theoretically, result in higher AA yields. Author summaryAcrylic acid is an economically important chemical compound due to its high market value. Nevertheless, the majority of acrylic acid consumed worldwide its produced from petroleum derivatives by a purely chemical process, which is not only expensive, but it also contributes towards environment deterioration. Hence, justifying the current need for sustainable novel production methods that allow higher profit margins. Ideally, to minimise production cust, the pathway should consist in the direct bio-based production from microbial feedstocks, such as Escherichia coli, but the current yields achieved are still to low to compete with conventional method. In this work, even though the glycerol pathway presented higher yields, we identified the malonyl-CoA route, when using glucose as carbon source, as having the most potential for industrial-scale production, since it is cheaper to implement. Furthermore, we also identified potential optimisation targets for all the tested pathways, that can help the bio-based method to compete with the conventional process.

bioengineering↗