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Lieven, C.

Publications and source records attributed to Lieven, C..

4 recordsLinked to original sources

A Genome-Scale Metabolic Model for the Smut-Fungus Ustilago maydis

Ustilago maydis is an important plant pathogen causing corn-smut disease and an effective biotechnological production host. The lack of a comprehensive metabolic overview hinders a full understanding of environmental adaptation and a full use of the organisms metabolic potential. Here, we report the first genome scale metabolic model (GSMM) of Ustilago maydis (iUma22) for the simulation of metabolic activities. iUma22 was reconstructed from sequencing and annotation using PathwayTools, the biomass equation was derived from literature values and from the codon composition. The final model contains over 25% of annotated genes in the sequenced genome. Substrate utilization was corrected by Biolog-Phenotype arrays and exponential batch cultivations were used to test growth predictions. A pan-genome of four different U. maydis strains revealed missing metabolic pathways in iUma22. The majority of metabolic differences between iUma22 and the pangenome occurs in the inositol, purine and starch metabolic pathways. The new model allows studies of metabolic adaptations to different environmental niches as well as for biotechnological applications.

systems biology↗

Memote: A community-driven effort towards a standardized genome-scale metabolic model test suite

Several studies have shown that neither the formal representation nor the functional requirements of genome-scale metabolic models (GEMs) are precisely defined. Without a consistent standard, comparability, reproducibility, and interoperability of models across groups and software tools cannot be guaranteed.\n\nHere, we present memote (https://github.com/opencobra/memote) an open-source software containing a community-maintained, standardized set of metabolic model tests. The tests cover a range of aspects from annotations to conceptual integrity and can be extended to include experimental datasets for automatic model validation. In addition to testing a model once, memote can be configured to do so automatically, i.e., while building a GEM. A comprehensive report displays the models performance parameters, which supports informed model development and facilitates error detection.\n\nMemote provides a measure for model quality that is consistent across reconstruction platforms and analysis software and simplifies collaboration within the community by establishing workflows for publicly hosted and version controlled models.

systems biology↗

A genome-scale metabolic model for Methylococcus capsulatus predicts reduced efficiency uphill electron transfer to pMMO.

BackgroundGenome-scale metabolic models allow researchers to calculate yields, to predict consumption and production rates, and to study the effect of genetic modifications in silico, without running resource-intensive experiments. While these models have become an invaluable tool for optimizing industrial production hosts like E. coli and S. cerevisiae, few such models exist for one-carbon (C1) metabolizers.\n\nResultsHere we present a genome-scale metabolic model for Methylococcus capsulatus, a well-studied obligate methanotroph, which has been used as a production strain of single cell protein (SCP). The model was manually curated, and spans a total of 877 metabolites connected via 898 reactions. The inclusion of 730 genes and comprehensive annotations, make this model not only a useful tool for modeling metabolic physiology, but also a centralized knowledge base for M. capsulatus. With it, we determined that oxidation of methane by the particulate methane monooxygenase is most likely driven through uphill electron transfer operating at reduced efficiency as this scenario matches best with experimental data from literature.\n\nConclusionsThe metabolic model will serve the ongoing fundamental research of C1 metabolism, and pave the way for rational strain design strategies towards improved SCP production processes in M. capsulatus.

systems biology↗

Cameo: A Python Library for Computer Aided Metabolic Engineering and Optimization of Cell Factories

Computational systems biology methods enable rational design of cell factories on a genomescale and thus accelerate the engineering of cells for the production of valuable chemicals and proteins. Unfortunately, for the majority of these methods implementations are either not published, rely on proprietary software, or do not provide documented interfaces, which has precluded their mainstream adoption in the field. In this work we present cameo, a platform-independent software that enables in silico design of cell factories and targets both experienced modelers as well as users new to the field. It is written in Python and implements state-of-the-art methods for enumerating and prioritizing knock-out, knock-in, over-expression, and down-regulation strategies and combinations thereof. Cameo is an open source software project and is freely available under the Apache License 2.0. A dedicated website including documentation, examples, and installation instructions can be found at http://cameo.bio. Users can also give cameo a try at http://try.cameo.bio.

bioengineering↗