Papers by Rainer Breitling
<p>The heat map shows relative maximal fluxes of the final biosynthetic step in the metabol... more <p>The heat map shows relative maximal fluxes of the final biosynthetic step in the metabolic pathways leading 15 different secondary metabolites, which were incorporated into the genome-scale metabolic models of 41 actinobacteria. Flux balance analysis was performed on the minimal medium described by Alam et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051511#pone.0051511-Alam1" target="_blank">[17]</a>. White indicates a high relative flux level, red indicates a low relative flux level (as % of the maximally obtained value across all species, displayed at the top of the figure). In the heatmap on the left, the number of model reactions and metabolites, the genome sizes and the number of secondary metabolite biosynthesis gene clusters (predicted using antiSMASH <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051511#pone.0051511-Medema4" target="_blank">[54]</a>) are plotted.</p
<p>The contour lines indicate when steady-state was reached (in minutes of simulated time).... more <p>The contour lines indicate when steady-state was reached (in minutes of simulated time). If steady-state was not reached before, simulations were stopped at 300 minutes (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002352#s3" target="_blank">Methods</a>). When a model did not reach steady-state before 300 minutes, the concentrations of pyruvate and/or 3-phosphoglycerate reached unreasonably high concentrations (black contour lines). Note that the models that do not reach steady-state within 300 minutes because of 3-PGA accumulation will eventually reach steady-state at very high 3-PGA concentrations if the simulations are run much longer. This is not the case for the models that show pyruvate accumulation. Since pyruvate kinase is not product-sensitive in the model, nothing stops the accumulation of pyruvate and steady state is never reached (see supplementary <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002352#pcbi.1002352.s002" target="_blank">Fig. S1</a> for example of simulations).</p
Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibli... more Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available in the Internet at http://dnb.d-nb.de. License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported license: CC-BY-NC-ND. In brief, this license authorizes each and everybody to share (to copy, distribute and transmit) the work under the following conditions, without impairing or restricting the authors' moral rights:
Metabolomics, the global characterization of metabolite profiles, is becoming an increasingly pow... more Metabolomics, the global characterization of metabolite profiles, is becoming an increasingly powerful tool for research on secondary metabolite discovery and production. In this review we discuss examples of recent technological advances and biological applications of metabolomics in the search for chemical novelty and the engineered production of bioactive secondary metabolites.
Bibliographic information published by the Deutsche
syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhib... more syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor
Arachnology, 2020
Eric Duffey's spider collection in the Manchester Museum, accumulated over more than 40 years, co... more Eric Duffey's spider collection in the Manchester Museum, accumulated over more than 40 years, contains more than 300 samples from a diverse range of biotopes in most South European countries. Most of this material was previously unsorted. It has now been sorted and identified to species level. It contains more than 2500 specimens of more than 500 species in 240 genera and 42 families. The collection details of all of these samples are listed here, and a number of selected specimens are illustrated.
<p>Time course simulation of model B, in which the reactions of the glycosomal PPP are swit... more <p>Time course simulation of model B, in which the reactions of the glycosomal PPP are switched on at <i>t</i> = 0 by increasing their V<sub>max</sub> value from zero to the value given in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003371#pcbi.1003371.s013" target="_blank">Table S1</a>. Glc<sub>e</sub> is 5 mM and <i>k<sub>TOX</sub></i> = 2 µl·min<sup>−1</sup>·mg protein<sup>−1</sup>. Solid lines indicate medians, shaded areas show interquartile ranges. Fluxes (J) are plotted on the left y-axis and are indicative of glucose uptake (GlcT<sub>plasma membrane</sub>), glycerol (GK) and pyruvate production (PyrT) and the two branches of pentose phosphate pathways (G6PDH<sub>c/g</sub>). The sum of bound phosphates in the glycosome (ΣP<sub>g</sub>), as exists in the model of glycolysis (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003371#pcbi-1003371-t002" target="_blank">Table 2</a>, moiety 5), is plotted on the right y-axis. Within 25 minutes, all bound phosphates within the glycosome are depleted and all metabolic fluxes subsequently drop to zero.</p
PLOS Computational Biology, 2013
<p>(<i>A</i>) The steady state flux through the cytosolic pentose phosphate pat... more <p>(<i>A</i>) The steady state flux through the cytosolic pentose phosphate pathway in model C as a function of the oxidative stress by varying the kinetic constant <i>k<sub>TOX</sub></i>. (<i>B</i>) Fluxes through the cytosolic PPP enzymes as a function of time upon sudden oxidative stress. During the whole time-course, <i>k<sub>TOX</sub></i> = 2 µl·min<sup>−1</sup> · mg protein<sup>−1</sup>. The system is removed from steady state at <i>t</i> = 0, by setting 99% of the NAD(P)H and trypanothione pools to the oxidized form. Shown is the relaxation of the cytosolic PPP fluxes. Solid lines indicate medians, shaded areas show interquartile ranges. Near identical results were obtained for model D (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003371#pcbi.1003371.s008" target="_blank">Figure S5</a>).</p
<p>(<i>A</i>) Detailed scheme of the modeled metabolic pathways. The numbered a... more <p>(<i>A</i>) Detailed scheme of the modeled metabolic pathways. The numbered arrows correspond to reactions from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003371#pcbi-1003371-t001" target="_blank">Table 1</a>. Extensions to the original model of glycolysis are indicated by colored shapes. Boundary metabolites are in bold, glycosomal Rib-5-P is a boundary metabolite in model C and D. (<i>B</i>) Schematic overview of the different models, each consisting of a unique combination of the colored modules described in (<i>A</i>) and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003371#pcbi-1003371-t001" target="_blank">Table 1</a>. Model C and D can alternatively utilize fructose (model C<sup>fru</sup> and D<sup>fru</sup>), but this branch is switched off unless specifically mentioned.</p
Communications Biology, 2019
The biosynthetic machinery responsible for the production of bacterial specialised metabolites is... more The biosynthetic machinery responsible for the production of bacterial specialised metabolites is encoded by physically clustered group of genes called biosynthetic gene clusters (BGCs). The experimental characterisation of numerous BGCs has led to the elucidation of subclusters of genes within BGCs, jointly responsible for the same biosynthetic function in different genetic contexts. We developed an unsupervised statistical method able to successfully detect a large number of modules (putative functional subclusters) within an extensive set of predicted BGCs in a systematic and automated manner. Multiple already known subclusters were confirmed by our method, proving its efficiency and sensitivity. In addition, the resulting large collection of newly defined modules provides new insights into the prevalence and putative biosynthetic role of these modular genetic entities. The automated and unbiased identification of hundreds of co-evolving group of genes is an essential breakthroug...
Trends in Biotechnology, 2017
Although there is still some scepticism within the biological community regarding the value and s... more Although there is still some scepticism within the biological community regarding the value and significance of quantitative computational modelling, important steps are continually being taken in order to enhance its accessibility and predictive power. We view these developments as essential components of an emerging "respectful modelling" framework, which has two critical aims: 1) Respecting the models themselves and facilitating the reproduction and update of modelling results by other scientists. 2) Respecting the predictions of the models, and rigorously quantifying the confidence associated with the modelling results. This respectful attitude will guide the design of higher-quality models and facilitate the use of models in modern applications, such as engineering and manipulating microbial metabolism by synthetic biology. Computational models in current research: Success and scepticism Quantitative computational models of cellular pathways and circuits are essential tools for generating clear, testable predictions about the behaviour of complex cellular machineries [1, 2]. Their use is currently moving beyond the proof-of-concept stage towards real-world applications, such as engineering and optimising biological microorganisms to produce specific chemicals and biofuels [3-5], as has been shown most successfully for various
Bioinformatics
Summary The Integrated Probabilistic Annotation (IPA) is an automated annotation method for LC–MS... more Summary The Integrated Probabilistic Annotation (IPA) is an automated annotation method for LC–MS-based untargeted metabolomics experiments that provides statistically rigorous estimates of the probabilities associated with each annotation. Here, we introduce ipaPy2, a substantially improved and completely refactored Python implementation of the IPA method. The revised method is now able to integrate tandem MS fragmentation data, which increases the accuracy of the identifications. Moreover, ipaPy2 provides a much more user-friendly interface, and isotope peaks are no longer treated as individual features but integrated into isotope fingerprints, greatly speeding up the calculations. The method has also been fully integrated with the mzMatch pipeline, so that the results of the annotation can be explored through the newly developed PeakMLViewerPy tool available at https://github.com/UoMMIB/PeakMLViewerPy. Availability and implementation The source code, extensive documentation, and ...
Analyzing complex networks is a difficult task, regardless of the chosen modeling framework. For ... more Analyzing complex networks is a difficult task, regardless of the chosen modeling framework. For a discrete regulatory network, even if the number of components is in some sense manageable, we have to deal with the problem of analyzing the dynamics in an exponentially large state space. A well known idea to approach this difficulty is to identify smaller building blocks of the system the study of which in isolation still renders information on the dynamics of the whole network. In this talk, we introduce the notion of symbolic steady state which allows us to identify such building blocks. We state explicit rules how to derive attractors of the network from subnetwork attractors valid for synchronous as well as asynchronous dynamics. Illustrating those rules, we derive general conditions for circuits embedded in the network to transfer their behavioral characteristics pertaining number and size of attractors observed in isolation to the complex network.
ACS Biomaterials Science & Engineering, 2015
Synthetic biology (SynBio) presents a new paradigm for how metabolic pathways can be designed, as... more Synthetic biology (SynBio) presents a new paradigm for how metabolic pathways can be designed, assembled and integrated within a cell. A key aim of SynBio is the development of orthogonal tools that facilitate the expression of heterologous genes and circuits in a non-native host (chassis). Compartmentalization represents one orthogonalization strategy, in particular for metabolic pathways, preventing unwanted protein-protein interactions and competition for resources with native pathways, while sequestering toxic intermediates and providing an appropriate environment to support metabolic channeling. A variety of biomaterials have been investigated for their ability to form intracellular compartments. Particularly versatile examples are bacterial microcompartments (BMCs), protein-based shells that sequester a multitude of metabolic reactions in their native host. These compartments provide a natural template for de novo compartmentalization and offer unprecedented opportunities for bioengineering using SynBio. Here we review BMCs as modular building blocks for a general compartmentalization
The small jumping spider Euophrys petrensis C. L. Koch, 1837 combines morphological characters of... more The small jumping spider Euophrys petrensis C. L. Koch, 1837 combines morphological characters of both Euophrys s. str. and Talavera, and its generic placement has consequently been contentious. After many years of being placed in Talavera, the species has recently been transferred back to Euophrys. Here, public DNA barcoding data are used to confirm that the species should be placed in the genus Talavera, as T. petrensis, stat. rev., as is also indicated by several putative morphological synapomorphies identified earlier.
Metabolic Engineering, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Papers by Rainer Breitling