A5020093183- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Carbohydrate Chemistry and Synthesis
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- Chemical Synthesis and Analysis
- Fungal Biology and Applications
- Polyamine Metabolism and Applications
- Microbial Metabolism and Applications
- Marine Sponges and Natural Products
- Plant-Microbe Interactions and Immunity
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- Synthetic Organic Chemistry Methods
- Glycosylation and Glycoproteins Research
- Plant Disease Resistance and Genetics
- Probiotics and Fermented Foods
- Enzyme Structure and Function
- Antibiotic Resistance in Bacteria
- Mycobacterium research and diagnosis
- Plant nutrient uptake and metabolism
- Enzyme Production and Characterization
- Biochemical and Structural Characterization
University of Tübingen
2016-2025
German Center for Infection Research
2016-2025
Czech Academy of Sciences, Institute of Microbiology
2025
Institute of Microbiology and Biotechnology
2017-2018
Boehringer Ingelheim (Germany)
2013
Instituto de Biotecnología de León
2012
University of Warwick
2012
Universidad de León
2012
Universidad de León
2012
Council of Science Editors
2009
Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining gene clusters that encode the biosynthetic pathways for these metabolites has become key methodology novel compound discovery. In 2011, we introduced antiSMASH, web server stand-alone tool automatic genomic identification analysis clusters, available at http://antismash.secondarymetabolites.org. Here, present version 3.0 which undergone major...
Non-ribosomal peptide synthetases (NRPSs) are large multimodular enzymes that synthesize a wide range of biologically active natural compounds, which many pharmacologically important. Peptide bond formation is catalyzed by the Condensation (C) domain. Various functional subtypes C domain exist: An LCL catalyzes between two L-amino acids, DCL links an acid to growing ending with D-amino acid, Starter (first denominated and classified as separate subtype here) acylates first amino...
We performed molecular phylogenetic analyses of glutamine synthetase (GS) genes in order to investigate their evolutionary history. The were done on 30 DNA sequences the GS gene which included both prokaryotes and eukaryotes. Two types are known at present: GSI found so far only GSII Our study has shown that two produced by a duplication preceded, perhaps > 1000 million years, divergence eukaryotes prokaryotes. results consistent with facts (i) is key enzyme nitrogen metabolism all extant...
ABSTRACT Seven complete genes and one incomplete gene for the biosynthesis of glycopeptide antibiotic balhimycin were isolated from producer, Amycolatopsis mediterranei DSM5908, by a reverse-cloning approach characterized. Using oligonucleotides derived glycosyltransferase sequences, 900-bp fragment was amplified used to identify DNA 9,882 bp. Of identified open reading frames, three ( oxyA - C ) showed significant sequence similarities cytochrome P450 monooxygenases bhaA halogenase, bgtfA...
Summary Streptomyces coelicolor GlnR is a global regulator that controls genes involved in nitrogen metabolism. By genomic screening 10 new targets were identified, including enzymes for ammonium assimilation ( glnII , gdhA ), nitrite reduction nirB urea cleavage ureA ) and number of biochemically uncharacterized proteins SCO0255 SCO0888 SCO2195 SCO2400 SCO2404 SCO7155 ). For the regulon, binding site which comprises sequence gTnAc‐n 6 ‐GaAAc‐n ‐GtnAC‐n ‐GAAAc‐n has been found. Reverse...
During the lifetime of a fermenter culture, soil bacterium S. coelicolor undergoes major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using specifically designed Affymetrix genechip and high-resolution time-series fermenter-grown samples. Surprisingly, we find that actually consists multiple finely orchestrated switching events. Strongly coherent clusters genes show drastic changes in already many hours before...
Mycobacterium tuberculosis can utilize various nutrients including nitrate as a source of nitrogen. Assimilation requires the reduction via nitrite to ammonium, which is then incorporated into metabolic pathways. This study was undertaken define molecular mechanism assimilation in M. tuberculosis. Homologues narGHJI-encoded reductase and nirBD-encoded have been found on chromosome Previous studies implied role for NarGHJI respiration rather than assimilation. Here, we show that narG mutant...
The expression of the structural gene (sacB) encoding Bacillus subtilis levansucrase in two gram-positive soil bacteria, Corynebacterium glutamicum ATCC 13032 and Streptomyces lividans 1326, was investigated. sacB presence sucrose is lethal to C. but not S. lividans. While secretes into medium, we could show that enzyme retained by cells. Our results imply can be used as a positive selection system coryneform bacteria.
Gene-inactivation studies point to the involvement of OxyB in catalyzing first oxidative phenol coupling reaction during glycopeptide antibiotic biosynthesis. The oxyB gene has been cloned and sequenced from vancomycin producer Amycolatopsis orientalis, hemoprotein produced Escherichia coli, crystallized, its structure determined 1.7-A resolution. gave UV-visible spectra characteristic a P450-like low spin ferric state. After reduction ferrous state by dithionite or spinach ferredoxin...
Summary Gamma‐butyrolactone signalling molecules are produced by many Streptomyces species, and several have been shown to regulate antibiotic production. In coelicolor A3(2) at least one γ‐butyrolactone (SCB1) has stimulate production, genes encoding proteins that involved in its synthesis ( scbA ) binding scbR characterized. Expression of these is autoregulated a complex mechanism involving the γ‐butyrolactone. this study, additional influenced ScbR were identified DNA microarray analysis,...
Summary Streptomyces coelicolor has an unusually large arsenal of glutamine synthetase (GS) enzymes: a prokaryotic GSI‐β‐subtype enzyme (encoded by glnA ), three annotated ‐like genes the GSI‐α‐subtype and eukaryote‐like II glnII ). Under all tested conditions, GSI was found to represent dominant activity. A significant heat‐labile GSII activity, which is very low undetectable in liquid‐grown cultures, only detected morphologically differentiating S. cultures. Analysis transcription S1...
Balhimycin, a vancomycin-type antibiotic from Amycolatopsis mediterranei, contains the unusual amino acid (S)-3,5-dihydroxyphenylglycine (Dpg), with an acetate-derived carbon backbone. After sequence analysis of biosynthetic gene cluster, one gene, dpgA, for predicted polyketide synthase (PKS) was identified, sharing 20-30% identity plant chalcone synthases. Inactivation dpgA resulted in loss balhimycin production, and restoration achieved by supplementation 3,5-dihydroxyphenylacetic acid,...
Linear and bicyclic glycopeptides occur as intermediates in the biosynthesis of aglycon glycopeptide antibiotics type shown. Considering structures these peptides those previously isolated analogues, sequence three oxidative ring-closing steps can be deduced for type-I type-II antibiotics. Thus, comprehensive insight into assembly is achieved first time.
Summary Pristinamycin, produced by Streptomyces pristinaespiralis Pr11, is a streptogramin antibiotic consisting of two chemically unrelated compounds, pristinamycin I and II. The semi‐synthetic derivatives these compounds are used in human medicine as therapeutic agents against methicillin‐resistant Staphylococcus aureus strains. Only the partial sequence biosynthetic gene cluster has been previously reported. To complete sequence, overlapping cosmids were isolated from S. Pr11 library...
Model mutants. The biosynthesis of glycopeptide antibiotics must be understood before it can reprogrammed to generate altered antibiotics. Based on a detailed HPLC-ESI-MS analysis linear and cyclic peptide intermediates balhimycin mutants, new model for assembly is suggested (see figure). We propose that the three central oxidative cyclizations by P450-dependant monooxygenases occur during cleavage from nonribosomal synthetase complex.