A5025072659- Microbial Metabolic Engineering and Bioproduction
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Protein Structure and Dynamics
- Metabolism and Genetic Disorders
- Microbial Community Ecology and Physiology
- Fungal and yeast genetics research
- Biofuel production and bioconversion
- Photosynthetic Processes and Mechanisms
- Biochemical Acid Research Studies
- Amino Acid Enzymes and Metabolism
- Mitochondrial Function and Pathology
- Enzyme Structure and Function
- Enzyme Catalysis and Immobilization
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Plant Stress Responses and Tolerance
- DNA Repair Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Machine Learning in Materials Science
- Innovative Microfluidic and Catalytic Techniques Innovation
Chalmers University of Technology
2015-2023
EnginZyme (Sweden)
2022
University of Technology
2021
University of Gothenburg
2017-2020
Institute for Biomedicine
2019
Cluster of Excellence on Plant Sciences
2015
Heinrich Heine University Düsseldorf
2012-2015
California Institute of Technology
2014
University of Cologne
2007-2013
Lund University
2007
Abstract Enzyme turnover numbers ( k cat ) are key to understanding cellular metabolism, proteome allocation and physiological diversity, but experimentally measured data sparse noisy. Here we provide a deep learning approach (DLKcat) for high-throughput prediction metabolic enzymes from any organism merely substrate structures protein sequences. DLKcat can capture changes mutated identify amino acid residues with strong impact on values. We applied this predict genome-scale values more than...
Abstract For most proteins annotated as enzymes, it is unknown which primary and/or secondary reactions they catalyze. Experimental characterizations of potential substrates are time-consuming and costly. Machine learning predictions could provide an efficient alternative, but hampered by a lack information regarding enzyme non-substrates, available training data comprises mainly positive examples. Here, we present ESP, general machine-learning model for the prediction enzyme-substrate pairs...
• In a previous transactivation screen, two Arabidopsis thaliana R2R3-MYB transcription factors, HAG2/MYB76 and HAG3/MYB29, along with the already characterized HAG1/MYB28, were identified as putative regulators of aliphatic glucosinolate biosynthesis. Molecular biochemical characterization HAG3/MYB29 functions was performed using transformants increased or repressed transcript levels. Real-time PCR assays, cotransformation assays measurements contents used to assess impact both MYB factors...
The photorespiratory pathway helps illuminated C(3)-plants under conditions of limited CO(2) availability by effectively exporting reducing equivalents in form glycolate out the chloroplast and regenerating glycerate-3-P as substrate for RubisCO. On other hand, this is considered probably futile because previously assimilated released mitochondria. Consequently, a lot effort has been made to reduce loss either fluxes via engineering RubisCO or circumventing mitochondrial release introduction...
Abstract During dark‐induced senescence isovaleryl‐CoA dehydrogenase (IVDH) and D‐2‐hydroxyglutarate ( D‐2HGDH ) act as alternate electron donors to the ubiquinol pool via electron‐transfer flavoprotein/electron‐transfer flavoprotein:ubiquinone oxidoreductase (ETF/ETFQO) pathway. However, role of this pathway in response other stresses still remains unclear. Here, we demonstrated that alternative is associated with tolerance drought Arabidopsis . In comparison wild type (WT) lines...
Enzymes that catalyze chemical reactions at high temperatures are used for industrial biocatalysis, applications in molecular biology, and as highly evolvable starting points protein engineering. The optimal growth temperature (OGT) of organisms is commonly to estimate the stability enzymes encoded their genomes, but number experimentally determined OGT values limited, particularly thermophilic organisms. Here, we report on development a machine learning model can accurately predict...
A synthesis of phenotypic and quantitative genomic traits is provided for bacteria archaea, in the form a scripted, reproducible workflow that standardizes merges 26 sources. The resulting unified dataset covers 14 traits, 5 4 environmental characteristics approximately 170,000 strain-level 15,000 species-aggregated records. It spans all habitats including soils, marine fresh waters sediments, host-associated thermal. Trait data can find use clarifying major dimensions ecological strategy...
Significance Archaerhodopsin-3 (Arch) is an integral membrane protein that can function as a genetically encoded fluorescent indicator of voltage in neurons. The ability to visualize changes great interest readout for neuronal activity. Published variants this protein, however, are too dim enable wide-field imaging cell populations. We used directed evolution increase the absolute brightness Arch reporter optogenetics research and live-cell imaging. This study establishes introducing...
The Michaelis constant K M describes the affinity of an enzyme for a specific substrate and is central parameter in studies kinetics cellular physiology. As measurements are often difficult time-consuming, experimental estimates exist only minority enzyme–substrate combinations even model organisms. Here, we build train organism-independent that successfully predicts values natural using machine deep learning methods. Predictions based on task-specific molecular fingerprint substrate,...
The Arabidopsis thaliana locus At5g06580 encodes an ortholog to Saccharomyces cerevisiae d-lactate dehydrogenase (AtD-LDH). recombinant protein is a homodimer of 59-kDa subunits with one FAD per monomer. A substrate screen indicated that AtD-LDH catalyzes the oxidation d- and l-lactate, d-2-hydroxybutyrate, glycerate, glycolate using cytochrome c as electron acceptor. shows clear preference for d-lactate, catalytic efficiency 200- 2000-fold higher than l-lactate glycolate, respectively, Km...
Glycolate, malate, lactate, and 2-hydroxyglutarate are important 2-hydroxy acids (2HA) in plant metabolism. Most of them can be found as D- L-stereoisomers. These 2HA play an integral role primary metabolism, where they involved fundamental pathways such photorespiration, tricarboxylic acid cycle, glyoxylate methylglyoxal pathway, lysine catabolism. Recent molecular studies Arabidopsis thaliana have helped elucidate the participation these metabolism physiology. In this chapter, we summarize...
The ambient temperature of all habitats is a key physical property that shapes the biology microbes inhabiting them. optimal growth (OGT) microbe, therefore piece data needed to understand evolutionary adaptations manifested in their genome sequence. Unfortunately there no database or easily downloadable dataset encompassing majority cultured microorganisms. We are thus limited interpreting genomic identify microbes. In this work I significantly contribute closing gap by mining from major...
Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and present study we use a genome-wide approach to precisely map location these. We find that are distributed evenly between heavy- light-strand mtDNA. The relative levels incorporated reflect polymerase γ discriminates four differentially during synthesis. observed pattern is also dependent on deoxyribonucleotide (dNTP) pools disease-causing mutations change these alter both absolute...
Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis adenosine triphosphate (ATP), but reason for glutamate excretion is unclear. Here, we dynamically profile uptake fluxes a liver cell line (HepG2) use genome-scale metabolic modeling in-depth analysis. We find that up 30%...
d-2-Hydroxyglutarate dehydrogenase (d-2HGDH) catalyzes the specific and efficient oxidation of d-2-hydroxyglutarate (d-2HG) to 2-oxoglutarate using FAD as a cofactor. In this work, we demonstrate that d-2HGDH localizes plant mitochondria its expression increases gradually during developmental dark-induced senescence in Arabidopsis thaliana, indicating an enhanced demand respiration alternative substrates through enzymatic system under these conditions. Using loss-of-function mutants...
Incorporation of ribonucleotides into DNA during genome replication is a significant source genomic instability. The frequency in determined by deoxyribonucleoside triphosphate/ribonucleoside triphosphate (dNTP/rNTP) ratios, the ability polymerases to discriminate against ribonucleotides, and capacity repair mechanisms remove incorporated ribonucleotides. To simultaneously compare how nuclear mitochondrial genomes incorporate we challenged these processes changing balance cellular dNTPs....
Only a small fraction of genes deposited to databases have been experimentally characterised. The majority proteins their function assigned automatically, which can result in erroneous annotations. reliability current annotations public is largely unknown; experimental attempts validate the accuracy within individual enzyme classes are lacking. In this study we performed an overview functional BRENDA database. We first applied high-throughput platform verify class S-2-hydroxyacid oxidases...
Extensive microdiversity within Prochlorococcus , the most abundant marine cyanobacterium, occurs at scales from a single droplet of seawater to ocean basins. To interpret structuring role variations in genetic potential, as well metabolic and physiological acclimation, we developed mechanistic constraint-based modeling framework that incorporates full suite genes, proteins, reactions, pigments, biochemical compositions 69 sequenced isolates spanning pangenome. Optimizing each strain local,...
Abstract Temperature is a fundamental environmental factor that shapes the evolution of organisms. Learning thermal determinants protein sequences in thus has profound significance for basic biology, drug discovery, and engineering. Here, we use data set over 3 million BRENDA enzymes labeled with optimal growth temperatures (OGTs) their source organisms to train deep neural network model (DeepET). The protein‐temperature representations learned by DeepET provide temperature‐related...
In roots of Arabidopsis (Arabidopsis thaliana), l-lactate is generated by the reduction pyruvate via dehydrogenase, but this enzyme does not efficiently catalyze reverse reaction. Here, we identify glycolate oxidase (GOX) paralogs GOX1, GOX2, and GOX3 as putative l-lactate-metabolizing enzymes based on their homology to CYB2, cytochrome c oxidoreductase from yeast Saccharomyces cerevisiae. We found that uses with a similar efficiency glycolate; in contrast, photorespiratory isoforms GOX1...