A5055779084- Microbial Metabolic Engineering and Bioproduction
- Biofuel production and bioconversion
- Fungal and yeast genetics research
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Enzyme Catalysis and Immobilization
- Advanced Proteomics Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Mass Spectrometry Techniques and Applications
- Probiotics and Fermented Foods
- Microbial Natural Products and Biosynthesis
- Particle accelerators and beam dynamics
- Particle Accelerators and Free-Electron Lasers
- Nuclear Physics and Applications
- Education and Teacher Training
- Resilience and Mental Health
- Amino Acid Enzymes and Metabolism
- Photosynthetic Processes and Mechanisms
- Youth Development and Social Support
- Viral gastroenteritis research and epidemiology
- Protein Structure and Dynamics
Novo Nordisk Foundation
2015-2024
Technical University of Denmark
2019-2024
Chr. Hansen (Denmark)
2023
Chalmers University of Technology
2015-2022
Novo Nordisk (Finland)
2021
Foundation Center
2015
Pontificia Universidad Católica de Chile
2014
Los Alamos National Laboratory
2004
Abstract Genome‐scale metabolic models ( GEM s) are widely used to calculate phenotypes. They rely on defining a set of constraints, the most common which is that production metabolites and/or growth limited by carbon source uptake rate. However, enzyme abundances and kinetics, act as limitations fluxes, not taken into account. Here, we present GECKO , method enhances account for enzymes part reactions, thereby ensuring each flux does exceed its maximum capacity, equal product enzyme's...
RAVEN is a commonly used MATLAB toolbox for genome-scale metabolic model (GEM) reconstruction, curation and constraint-based modelling simulation. Here we present Toolbox 2.0 with major enhancements, including: (i) de novo reconstruction of GEMs based on the MetaCyc pathway database; (ii) redesigned KEGG-based pipeline; (iii) convergence reconstructions from various sources; (iv) improved performance, usability, compatibility COBRA Toolbox. Capabilities are here illustrated through...
Abstract Genome-scale metabolic models (GEMs) represent extensive knowledgebases that provide a platform for model simulations and integrative analysis of omics data. This study introduces Yeast8 an associated ecosystem comprehensive computational resource performing the metabolism Saccharomyces cerevisiae ––an important organism widely used cell-factory. tracks community development with version control, setting standard how GEMs can be continuously updated in simple reproducible way. We...
Through advanced mechanistic modeling and the generation of large high-quality datasets, machine learning is becoming an integral part understanding engineering living systems. Here we show that models can be combined to enable accurate genotype-to-phenotype predictions. We use a genome-scale model pinpoint targets, efficient library construction metabolic pathway designs, high-throughput biosensor-enabled screening for training diverse algorithms. From single data-generation cycle, this...
Abstract Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration enzyme constraints proteomics data into such was first enabled by GECKO toolbox, allowing study phenotypes constrained protein limitations. Here, we upgrade toolbox in order to enhance with any organism a compatible GEM reconstruction. With this, enzyme-constrained budding yeasts Saccharomyces cerevisiae , Yarrowia lipolytica...
Heme is an oxygen carrier and a cofactor of both industrial enzymes food additives. The intracellular level free heme low, which limits the synthesis proteins. Therefore, increasing allows increased production Using genome-scale metabolic model (GEM) Yeast8 for yeast Saccharomyces cerevisiae , we identified fluxes potentially important to synthesis. With this model, in silico simulations highlighted 84 gene targets balancing biomass production. Of those identified, 76 genes were individually...
Saccharomyces cerevisiae is a widely used cell factory; therefore, it important to understand how organizes key functional parts when cultured under different conditions. Here, we perform multiomics analysis of S. by culturing the strain with wide range specific growth rates using glucose as sole limiting nutrient. Under these conditions, measure absolute transcriptome, proteome, phosphoproteome, and metabolome. Most protein groups show linear dependence on rate. Proteins engaged in...
Abstract Several studies have shown that neither the formal representation nor functional requirements of genome-scale metabolic models (GEMs) are precisely defined. Without a consistent standard, comparability, reproducibility, and interoperability across groups software tools cannot be guaranteed. Here, we present memote ( https://github.com/opencobra/memote ) an open-source containing community-maintained, standardized set me tabolic mo del te sts. The tests cover range aspects from...
A recurrent problem in genome-scale metabolic models (GEMs) is to correctly represent lipids as biomass requirements, due the numerous of possible combinations individual lipid species and corresponding lack fully detailed data. In this study we present SLIMEr, a formalism for representing requirements GEMs using commonly available experimental SLIMEr enhances GEM with mathematical constructs where Split Lipids Into Measurable Entities (SLIME reactions), addition constraints on both classes...
Engineering Saccharomyces cerevisiae for industrial-scale production of valuable chemicals involves extensive modulation its metabolism. Here, we identified novel gene expression fine-tuning set-ups to enhance endogenous metabolic fluxes toward increasing levels acetyl-CoA and malonyl-CoA. dCas9-based transcriptional regulation was combined together with a malonyl-CoA responsive intracellular biosensor select beneficial set-ups. The candidate genes screening were predicted using genome-scale...
ABSTRACT The field of metabolic modelling at the genomescale continues to grow with more models being created and curated. This comes an increasing demand for adopting common principles regarding transparency versioning, in addition standardisation efforts file formats, annotation testing. Here, we present a standardised template git-based GitHub-hosted genome-scale (GEMs) supporting both new curated ones, following FAIR (findability, accessibility, interoperability, reusability),...
Abstract RAVEN is a commonly used MATLAB toolbox for genome-scale metabolic model (GEM) reconstruction, curation and constraint-based modelling simulation. Here we present Toolbox 2.0 with major enhancements, including: (i) de novo reconstruction of GEMs based on the MetaCyc pathway database; (ii) redesigned KEGG-based pipeline; (iii) convergence reconstructions from various sources; (iv) improved performance, usability, compatibility COBRA Toolbox. Capabilities are here illustrated through...
Abstract Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration enzyme constraints proteomics data into GEMs was first enabled by GECKO method, allowing study phenotypes constrained protein limitations. Here, we upgraded toolbox in order to enhance with any organism an available GEM reconstruction. With this, enzyme-constrained (ecModels) budding yeasts Saccharomyces cerevisiae, Yarrowia...
Protein quantification via label-free mass spectrometry (MS) has become an increasingly popular method for predicting genome-wide absolute protein abundances. A known caveat of this approach, however, is the poor technical reproducibility, that is, how consistent predictions are when same sample measured repeatedly. Here, we proteomics data Saccharomyces cerevisiae with both biological and inter-batch triplicates, to analyze accuracy precision MS. Moreover, analyzed these metrics vary...
Parageobacillus thermoglucosidasius represents a thermophilic, facultative anaerobic bacterial chassis, with several desirable traits for metabolic engineering and industrial production. To further optimize strain productivity, systems level understanding of its metabolism is needed, which can be facilitated by genome-scale model. Here, we present p-thermo, the most complete, curated validated model (to date) NCIMB 11955. It spans total 890 metabolites, 1175 reactions 917 genes, forming an...
Biological functions are orchestrated by intricate networks of interacting genetic elements. Predicting the interaction landscape remains a challenge for systems biology and new research tools allowing simple rapid mapping sequence to function desirable. Here, we describe CRI-SPA, method transfer chromosomal features from CRI-SPA Donor strain arrayed strains in large libraries Saccharomyces cerevisiae. is based on mating, CRISPR-Cas9-induced gene conversion, Selective Ploidy Ablation. can be...
The yeast Saccharomyces cerevisiae is an attractive microbial host for industrial production and used widely manufacturing, e.g., pharmaceuticals. Chemostat cultivation mode efficient strategy processes as it ensures a constant, well-controlled environment.
Unstructured, dynamic bioreactor models of complex processes usually possess many nonidentifiable, insensitive, or statistically nonsignificant parameters. However, an exhaustive search to find a reduced set identifiable parameters is computationally demanding. We developed heuristic iterative procedure for parameter optimization (HIPPO), generic and free symbolic mathematical manipulations, help bioprocess engineers estimate significant parameters, thus obtaining reliable models. This...
Summary Debaryomyces hansenii is a non‐conventional yeast considered to be well‐suited option for number of different industrial bioprocesses. It exhibits set beneficial traits (halotolerant, oleaginous, xerotolerant, inhibitory compounds resistant) which translates advantages fermentation setups when compared traditional hosts. Although D. has been highly studied during the last three decades, especially in regards its salt‐tolerant character, molecular mechanisms underlying this natural...