A5103130326- Microbial Metabolic Engineering and Bioproduction
- Plant biochemistry and biosynthesis
- Biofuel production and bioconversion
- CRISPR and Genetic Engineering
- Metabolomics and Mass Spectrometry Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Proteomics Techniques and Applications
- Microbial Community Ecology and Physiology
- Fungal and yeast genetics research
- Genomics and Phylogenetic Studies
- Enzyme Catalysis and Immobilization
- Chemical synthesis and alkaloids
- Photosynthetic Processes and Mechanisms
- Microbial Natural Products and Biosynthesis
- Biochemical and biochemical processes
- Enterobacteriaceae and Cronobacter Research
- Parvovirus B19 Infection Studies
- Plant Molecular Biology Research
- Amino Acid Enzymes and Metabolism
- Analytical Chemistry and Chromatography
- Tryptophan and brain disorders
- Bacterial Genetics and Biotechnology
- Plant Gene Expression Analysis
- Fungal Biology and Applications
- Sirtuins and Resveratrol in Medicine
Novo Nordisk Foundation
2015-2024
Technical University of Denmark
2015-2024
Foundation Center
2016
Abstract Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine 1 . As MIAs difficult to chemically synthesize, world’s supply chain for relies on low-yielding extraction purification precursors vindoline catharanthine from Catharanthus roseus , which is then followed by simple in vitro chemical coupling reduction form at an industrial scale...
Yeast Saccharomyces cerevisiae was engineered for de novo production of six different flavonoids (naringenin, liquiritigenin, kaempferol, resokaempferol, quercetin, and fisetin) directly from glucose, without supplementation expensive intermediates. This required reconstruction long biosynthetic pathways, comprising up to eight heterologous genes plants. The obtained titers kaempferol 26.57±2.66mgL-1 quercetin 20.38±2.57mgL-1 exceed the previously reported in yeast. is also first report...
Abstract Stilbenoids, including resveratrol and its methylated derivatives, are natural potent antioxidants, produced by some plants in trace amounts as defense compounds. Extraction of stilbenoids from sources is costly due to their low abundance often limited availability the plant. Here we engineered yeast Saccharomyces cerevisiae for production on a simple mineral medium typically used industrial production. We applied pull-push-block strain engineering strategy that included...
Advances in synthetic biology and our understanding of the rules promoter architecture have led to development diverse constitutive inducible promoters eukaryotes prokaryotes. However, design by specific endogenous or environmental conditions is still rarely undertaken. In this study, we engineered characterized a set strong, for budding yeast Saccharomyces cerevisiae that are under acidic (pH ≤ 3). Using available expression transcription factor binding data, literature on transcriptional...
Psilocybin is a tryptamine-derived psychoactive alkaloid found mainly in the fungal genus Psilocybe, among others, and active ingredient so-called "magic mushrooms". Although its notoriety originates from psychotropic properties popular use as recreational drug, clinical trials have recently recognized psilocybin promising candidate for treatment of various psychological neurological afflictions. In this work, we demonstrate de novo biosynthetic production related tryptamine derivatives...
Terpenoids are a diverse group of over 55,000 compounds with potential applications as advanced fuels, bulk and fine chemicals, pharmaceutical ingredients, agricultural etc. To facilitate their bio-based production, there is need for plug-and-play hosts, capable high-level production different terpenoids. Here we engineer Y. lipolytica platform strains the overproduction mono-, sesqui-, di-, tri-, tetraterpenoids. The monoterpene strain was evaluated by expressing Perilla frutescens limonene...
We present a selection design that couples S-adenosylmethionine–dependent methylation to growth. demonstrate its use in improving the enzyme activities of not only N-type and O-type methyltransferases by 2-fold but also an acetyltransferase another category when linked pathway Escherichia coli using adaptive laboratory evolution. application for drug discovery catechol O-methyltransferase inhibitors entacapone tolcapone. Implementation this Saccharomyces cerevisiae is demonstrated.
The application of small amounts natural plant growth hormones, such as gibberellins (GAs), can increase the productivity and quality many vegetable fruit crops. However, gibberellin hormones usage is limited by high cost their production, which currently based on fermentation a fungal producer Fusarium fujikuroi that produces mix several GAs. We explored potential oleaginous yeast Yarrowia lipolytica to produce specific profiles Firstly, production GA-precursor ent-kaurenoic acid (KA) at...
Abscisic acid (ABA) is a phytohormone with applications in agriculture and human health. ABA can be produced by Botrytis cinerea, plant pathogenic filamentous fungus. However, the cultivation process lengthy strain improvement genetic engineering difficult. Therefore, we engineered oleaginous yeast Yarrowia lipolytica as an alternative host for production. First, expressed five B. cinerea genes involved biosynthesis (BcABA1,BcABA2,BcABA3,BcABA4 BcCPR1) Y. chassis optimized mevalonate flux....
Rosmarinic acid is a hydroxycinnamic ester commonly found in the Boraginaceae and Lamiaceae plant families. It exhibits various biological activities, including antioxidant, anti-inflammatory, antibacterial, antiallergic, antiviral properties. used as food cosmetic ingredient, several pharmaceutical applications have been suggested well. currently produced by extraction from plants or chemical synthesis; however, due to limited availability of sources complexity synthesis method, there an...
Technological advances in high-resolution mass spectrometry (MS) vastly increased the number of samples that can be processed a life science experiment, as well volume and complexity generated data. To address bottleneck high-throughput data processing, we present SmartPeak (https://github.com/AutoFlowResearch/SmartPeak), an application encapsulates advanced algorithms to enable fast, accurate, automated processing capillary electrophoresis–, gas chromatography–, liquid chromatography...
The yeast Saccharomyces cerevisiae is widely used in industrial biotechnology for the production of fuels, chemicals, food ingredients, and beverages, pharmaceuticals. To obtain high-performing strains such bioprocesses, it often necessary to test tens or even hundreds metabolic engineering targets, preferably combinations, account synergistic antagonistic effects. Here, we present a method that allows simultaneous perturbation multiple selected genetic targets by combining advantage...
Abstract The indole scaffold is a recurring structure in multiple bioactive heterocycles and natural products. Substituted indoles like the amino acid tryptophan serve as precursor for wide range of products with pharmaceutical or agrochemical applications. Inspired by versatility these compounds, medicinal chemists have decades exploited core drug discovery process. With aim tuning properties lead candidates, regioselective halogenation common strategy. However, chemical generally...
Bio-conversion of lignocellulosic biomass to high-value products offers numerous benefits; however, its development is hampered by chemical inhibitors generated during the pretreatment process. A better understanding how microbes naturally respond those valuable in process designing microorganisms with improved tolerance. Pseudomonas taiwanensis VLB120 a natively tolerant strain that utilizes wide range carbon sources including pentose and hexose sugars. To this end, we investigated...
Absolute quantification of free intracellular metabolites is a valuable tool in both pathway discovery and metabolic engineering. In this study, we conducted comprehensive examination different hot cold combined quenching/extraction approaches to extract quantify Pseudomonas taiwanensis (P. taiwanensis) VLB120 provide useful reference data set absolute metabolite concentrations. The suitability commonly used metabolomics tools including pressure driven fast filtration system followed by...
While Pseudomonas has the capability for high metabolic activity and provision of reduced redox cofactors important biocatalytic applications, exploitation this characteristic might be hindered by high, constitutive and, consequently, competition with NADH dehydrogenases respiratory chain. The in-depth analysis dehydrogenase mutants taiwanensis VLB120 presented here provides insight into phenotypic response strain to these metabolism perturbations. This degree flexibility needs taken account...
Bacteria in the gastrointestinal tract play a crucial role intestinal motility, homeostasis, and dysfunction. Unraveling mechanisms by which microbes impact host poses many challenges due to extensive array of metabolites produced or metabolized bacteria gut. Here, we describe engineering gut commensal bacterium,
Abstract Obligate aerobic organisms rely on a functional electron transport chain for energy generation and NADH oxidation. Because of this essential requirement, the genes pathway are likely constitutively highly expressed to avoid cofactor imbalance shortage under fluctuating environmental conditions. We here investigated essentiality three dehydrogenases respiratory obligate aerobe Pseudomonas taiwanensis VLB120 impact knockouts corresponding its physiology metabolism. While mutant...