Biology subjects

Ebert, B. E.

Publications and source records attributed to Ebert, B. E..

3 recordsLinked to original sources

bioRxiv2018

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↗

bioRxiv2018

Determination of growth-coupling strategies and their underlying principles

Metabolic coupling of product synthesis and microbial growth is a prominent approach for maximizing production performance. Growth-coupling (GC) also helps stabilizing target production and allows the selection of superior production strains by adaptive laboratory evolution. We have developed the computational tool gcOpt, which identifies knockout strategies leading to the best possible GC by maximizing the minimally guaranteed product yield. gcOpt implicitly favors solutions resulting in strict coupling of product synthesis to growth and metabolic activity while avoiding solutions inferring weak, conditional coupling.\n\nGC intervention strategies identified by gcOpt were examined for GC generating principles under diverse conditions. Curtailing the metabolism to render product formation an essential carbon drain was identified as one major strategy generating strong coupling of metabolic activity and target synthesis. Impeding the balancing of cofactors and protons in the absence of target production was the underlying principle of all other strategies and further increased the GC strength of the aforementioned strategies. Thus, generating a dependency between supply of global metabolic cofactors and product synthesis appears to be advantageous in enforcing strong GC.\n\nAbbreviations

systems biology↗

bioRxiv2017

Discovery and Evaluation of Biosynthetic Pathways for the Production of Five Methyl Ethyl Ketone Precursors

The limited supply of fossil fuels and the establishment of new environmental policies shifted research in industry and academia towards sustainable production of the 2nd generation of biofuels, with Methyl Ethyl Ketone (MEK) being one promising fuel candidate. MEK is a commercially valuable petrochemical with an extensive application as a solvent. However, as of today, a sustainable and economically viable production of MEK has not yet been achieved despite several attempts of introducing biosynthetic pathways in industrial microorganisms. We used BNICE.ch as a retrobiosynthesis tool to discover all novel pathways around MEK. Out of 1325 identified compounds connecting to MEK with one reaction step, we selected 3-oxopentanoate, but-3-en-2-one, but-1-en-2-olate, butylamine, and 2-hydroxy-2-methyl-butanenitrile for further study. We reconstructed 3679610 novel biosynthetic pathways towards these 5 compounds. We then embedded these pathways into the genome-scale model of E. coli, and a set of 18622 were found to be most biologically feasible ones based on thermodynamics and their yields. For each novel reaction in the viable pathways, we proposed the most similar KEGG reactions, with their gene and protein sequences, as candidates for either a direct experimental implementation or as a basis for enzyme engineering. Through pathway similarity analysis we classified the pathways and identified the enzymes and precursors that were indispensable for the production of the target molecules. These retrobiosynthesis studies demonstrate the potential of BNICE.ch for discovery, systematic evaluation, and analysis of novel pathways in synthetic biology and metabolic engineering studies.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC=\"FIGDIR/small/209569_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (27K):\norg.highwire.dtl.DTLVardef@15bb5corg.highwire.dtl.DTLVardef@bfc12borg.highwire.dtl.DTLVardef@1230500org.highwire.dtl.DTLVardef@1d74d2_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

synthetic biology↗