A5043498172- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Fungal Biology and Applications
- Plant biochemistry and biosynthesis
- Microbial Metabolic Engineering and Bioproduction
- Mycotoxins in Agriculture and Food
- Analytical Chemistry and Chromatography
- Plant Pathogens and Fungal Diseases
- Genomics and Phylogenetic Studies
- Metabolomics and Mass Spectrometry Studies
- Microbial Metabolism and Applications
- Species Distribution and Climate Change
- CRISPR and Genetic Engineering
- Microbial Community Ecology and Physiology
- Glycosylation and Glycoproteins Research
- Spectroscopy and Chemometric Analyses
- Sesquiterpenes and Asteraceae Studies
- Plant-Microbe Interactions and Immunity
- Insect symbiosis and bacterial influences
- Plant tissue culture and regeneration
- Plant Molecular Biology Research
- Plant Reproductive Biology
- RNA and protein synthesis mechanisms
- Isotope Analysis in Ecology
- Chromatography in Natural Products
Technical University of Denmark
2014-2022
Novo Nordisk Foundation
2019-2022
Ecologie Microbienne Lyon
2012
Biosynthetic pathways of secondary metabolites from fungi are currently subject to an intense effort elucidate the genetic basis for these compounds due their large potential within pharmaceutics and synthetic biochemistry. The preferred method is methodical gene deletions identify supporting enzymes key synthases one cluster at a time. In this study, we design apply DNA expression array Aspergillus nidulans in combination with legacy data form comprehensive compendium. We...
Streptomycetes serve as major producers of various pharmacologically and industrially important natural products. Although CRISPR-Cas9 systems have been developed for more robust genetic manipulations, concerns genome instability caused by the DNA double-strand breaks (DSBs) toxicity Cas9 remain. To overcome these limitations, here we report development DSB-free, single-nucleotide–resolution editing system CRISPR-BEST (CRISPR-Base Editing SysTem), which comprises a cytidine (CRISPR-cBEST) an...
In natural-product drug discovery, finding new compounds is the main task, and thus fast dereplication of known essential. This usually performed by manual liquid chromatography-ultraviolet (LC-UV) or visible light-mass spectroscopy (Vis-MS) interpretation detected peaks, often assisted automated identification previously identified compounds. We used a 15 min high-performance chromatography-diode array detection (UHPLC-DAD)-high-resolution MS method (electrospray ionization (ESI)(+)...
In drug discovery, reliable and fast dereplication of known compounds is essential for identification novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadrupole time flight mass spectrometry (UHPLC-DAD-QTOFMS) providing both accurate full-scan (MS) tandem high resolution MS (MS/HRMS) data. The methodology was demonstrated on from marine-derived strains Aspergillus, Penicillium, Emericellopsis, including...
Microorganisms are a rich source of bioactives; however, chemical identification is major bottleneck. Strategies that can prioritize the most prolific microbial strains and novel compounds great interest. Here, we present an integrated approach to evaluate biosynthetic richness in bacteria mine associated diversity. Thirteen closely related Pseudoalteromonas luteoviolacea isolated from all over Earth were analyzed using untargeted metabolomics strategy, metabolomic profiles correlated with...
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....
Filamentous fungi are a rich source of bioactive compounds, ranging from statins over immunosuppressants to antibiotics. The coupling genes metabolites is large commercial interest for production the bioactives future. To this end, we have investigated use stable isotope labeled amino acids (SILAAs). SILAAs were added cultivation media filamentous fungus Aspergillus nidulans study cyclic tetrapeptide nidulanin A. Analysis by UHPLC-TOFMS confirmed that incorporated into produced A, and change...
To accelerate the shift to bio-based production and overcome complicated functional implementation of natural artificial biosynthetic pathways industry relevant organisms, development new, versatile, platforms is required. Here we present a novel yeast-based platform for biosynthesis bacterial aromatic polyketides. The based on synthetic polyketide synthase system enabling first demonstration in eukaryotic host.
We present the results from stable isotope labeled precursor feeding studies combined with ultrahigh performance liquid chromatography-high resolution mass spectrometry for identification of polyketide (PK) end-products. Feeding experiments were performed 13C8-6-methylsalicylic acid (6-MSA) and 13C14-YWA1, both produced in-house, as well commercial 13C7-benzoic 2H7-cinnamic acid, in species Fusarium, Byssochlamys, Aspergillus, Penicillium. Incorporation 6-MSA into terreic or patulin was not...
Actinomycetes make a wealth of complex, structurally diverse natural products, and key challenge is to link them their biosynthetic gene clusters delineate the reactions catalyzed by each enzymes. Here, we report cluster for pyracrimycin A, set nine genes that includes core nonribosomal peptide synthase (pymB) utilizes serine proline as precursors monooxygenase (pymC) catalyzes Baeyer–Villiger oxidation. The similar one brabantamide A; however, A biosynthesis differs in feeding experiments...
Abstract Filamentous actinomycetes serve as major producers of various natural products including antimicrobial compounds. Although CRISPR-Cas9 systems have been developed for more robust genetic manipulations, concerns genome instability caused by the DNA double-strand breaks (DSB) and toxicity Cas9 remain. To overcome these limitations, here we report development DSB-free, single-nucleotide resolution editing system CRISPR-BEST ( CRISPR - B ase E diting S ys T em). Specifically targeted an...
Abstract To accelerate the shift to bio-based production and overcome complicated functional implementation of natural artificial biosynthetic pathways industry relevant organisms, development new, versatile, platforms is required. Here we present a novel yeast platform for biosynthesis bacterial aromatic polyketides. The based on synthetic polyketide synthase system enabling first demonstration in eukaryotic host.
We have elucidated the mode of biosynthesis meroterpenoid compound Yanuthone D in Aspergillus niger. successfully deleted all cluster genes, and identified a number intermediates. Structures intermediates were solved using combined approach comprising classical 1D- 2D-NMR tandem mass spectrometry (MS/MS). In this study we confirmed that is origin, an unexpected precursor, which has not before been reported for
Fungi are a valuable source of metabolites and other bioactive compounds. These compounds essential for human society, it is estimated that around 49% the drugs used to treat cancer natural products or derived therefrom.