A5063129265- Microbial Natural Products and Biosynthesis
- Carbohydrate Chemistry and Synthesis
- Genomics and Phylogenetic Studies
- Synthetic Organic Chemistry Methods
- Marine Sponges and Natural Products
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Plant-Microbe Interactions and Immunity
- Chemical Synthesis and Analysis
- Plant Disease Resistance and Genetics
- Bioactive Compounds and Antitumor Agents
- Enzyme Production and Characterization
- Microbial Metabolism and Applications
- Cancer therapeutics and mechanisms
- Fungal Biology and Applications
- Antibiotic Resistance in Bacteria
- Plant Pathogens and Fungal Diseases
- Synthesis and Biological Activity
- RNA modifications and cancer
- Biochemical and Molecular Research
- DNA and Nucleic Acid Chemistry
- Bacteriophages and microbial interactions
- Microbial Metabolic Engineering and Bioproduction
- Plant biochemistry and biosynthesis
- Cancer-related Molecular Pathways
Universidad de Oviedo
2015-2024
Instituto de Investigación Sanitaria del Principado de Asturias
2001-2024
NIHR Southampton Biomedical Research Centre
2022
Janssen (Belgium)
2022
Technical University of Munich
2022
University of Southampton
2022
University of Kentucky
1968-2008
Unidades Centrales Científico-Técnicas
2007
Consejo Superior de Investigaciones Científicas
2007
University of Freiburg
2002-2004
Streptomyces albus J1074 is a streptomycete strain widely used as host for expression of secondary metabolite gene clusters. Bioinformatic analysis the genome this organism predicts presence 27 clusters metabolites. We have three different strategies activation some these silent/cryptic in S. J1074: two hybrid polyketide-non-ribosomal peptides (PK-NRP) (antimycin and 6-epi-alteramides), type I PK (candicidin), non-ribosomal (NRP) (indigoidine) glycosylated compounds (paulomycins). By...
Rebeccamycin and staurosporine are natural products with antitumor properties, which belong to the family of indolocarbazole alkaloids. An intense effort currently exists for generation derivatives treatment several diseases, including cancer neurodegenerative disorders. Here, we report a biological process based on combinatorial biosynthesis production compounds (or their precursors) in engineered microorganisms as complementary approach chemical synthesis. We have dissected reconstituted...
ABSTRACT Mithramycin is an antitumor polyketide drug produced by Streptomyces argillaceus that contains two deoxysugar chains, a disaccharide consisting of d -olivoses and trisaccharide -olivose, -oliose, -mycarose. From cosmid clone (cosAR3) which confers resistance to mithramycin in streptomycetes, 3-kb Pst I- Xho I fragment was sequenced, divergent genes ( mtmGI mtmGII ) were identified. Comparison the deduced products both with proteins databases showed similarities glycosyltransferases...
Abstract Thiocoraline is a thiodepsipeptide antitumor compound produced by two actinomycetes Micromonospora sp. ACM2‐092 and ML1, isolated from marine invertebrates (a soft coral mollusc) found of the Indian Ocean coast Mozambique. By using oligoprimers derived nonribosomal peptide synthetase (NRPS) consensus sequences, six PCR fragments containing putative NRPS adenylation domains were amplified chromosome ML1. Insertional inactivation each domain showed that them generated nonproducing...
A 5.2 kb region from the oleandomycin gene cluster in Streptomyces antibioticus located between polyketide synthase and sugar biosynthetic genes was cloned. Sequence analysis revealed presence of three open reading frames (designated oleI , oleN2 oleR ). The product resembled glycosyltransferases involved macrolide inactivation including oleD product, a previously described glycosyltransferase S. . showed similarities with different aminotransferases biosynthesis 6‐deoxyhexoses. similar to...
The biosynthetic pathways for violacein and indolocarbazoles (rebeccamycin, staurosporine) include a decarboxylative fusion of two tryptophan units. However, in the case violacein, one tryptophans experiences an unusual 1-->2 shift indole ring. gene cluster was previously reported to consist four genes, vioABCD. Here we studied pathway through expression vio genes Escherichia coli Streptomyces albus. A pair (vioAB), responsible earliest steps biosynthesis, functionally equivalent homologous...
Summary The indolocarbazole staurosporine is a potent inhibitor of variety protein kinases. It contains sugar moiety attached through C‐N linkages to both indole nitrogen atoms the core. Staurosporine biosynthesis was reconstituted in vivo heterologous host Streptomyces albus by using two different plasmids: ‘aglycone vector’ expressing set genes involved together with staG (encoding glycosyltransferase) and/or staN (coding for P450 oxygenase), and ‘sugar responsible moiety. Attachment...
Mithramycin is an antitumor compound produced by Streptomyces argillaceus that has been used for the treatment of several types tumors and hypercalcaemia processes. However, its use in humans limited because side effects. Using combinatorial biosynthesis approaches, we have generated seven new mithramycin derivatives, which differ from parental sugar profile or both 3-side chain. From these studies three novel derivatives were identified, demycarosyl-3D-β-d-digitoxosylmithramycin SK,...
The World Health Organization warns that the alarming increase in antibiotic resistant bacteria will lead to 2.7 million deaths annually due lack of effective therapies. Clearly, there is an urgent need for short-term alternatives help alleviate these figures. In this respect, scientific community exploring neglected ecological niches from which prototypical antibiotic-producing Streptomycetes are expected be present. Recent studies have reported honeybees and their products carry...
To gain initial structure−activity relationships regarding the highly functionalized pentyl side chain attached at C-3 of mithramycin (MTM), we focused on a post-polyketide synthase (post-PKS) tailoring step MTM biosynthesis by Streptomyces argillaceus ATCC 12956, which was proposed to be catalyzed ketoreductase (KR) MtmW. In this last biosynthesis, keto group is reduced secondary alcohol, and anticipated generation an derivative with additional in 3-side chain. Insertional inactivation...