A5059026894- Microbial Natural Products and Biosynthesis
- Carbohydrate Chemistry and Synthesis
- Genomics and Phylogenetic Studies
- Synthetic Organic Chemistry Methods
- Marine Sponges and Natural Products
- Plant-Microbe Interactions and Immunity
- Glycosylation and Glycoproteins Research
- Plant Disease Resistance and Genetics
- Microbial Metabolism and Applications
- Cancer therapeutics and mechanisms
- Fungal Biology and Applications
- Bioactive Compounds and Antitumor Agents
- Synthesis and Biological Activity
- Plant Pathogens and Fungal Diseases
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- Probiotics and Fermented Foods
- RNA and protein synthesis mechanisms
- Enzyme Production and Characterization
- Mycobacterium research and diagnosis
- Steroid Chemistry and Biochemistry
- Synthesis and Catalytic Reactions
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Structure and Function
Universidad de Oviedo
2013-2023
Instituto de Investigación Sanitaria del Principado de Asturias
2018-2020
Clinical and Laboratory Standards Institute
2017
University of Kentucky
2002-2008
University of Freiburg
2002
Medical University of South Carolina
2002
NOAA National Ocean Service
2002
Instituto de Productos Lácteos de Asturias
1998
Massachusetts Institute of Technology
1983-1986
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...
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...
Plasmid-borne resistance to fosfomycin in bacteria is due modification of the antibiotic molecule by a glutathione S-transferase that catalyzes formation covalent bond between sulfhydryl residue cysteine and C-1 fosfomycin. This reaction results opening epoxide ring form an inactive adduct, structure which was confirmed nuclear magnetic resonance. Dialyzed extracts prepared from resistant Escherichia coli strains were unable modify unless exogenous added mixtures. Similarly, mutants...
Summary Interaction of the predatory myxobacterium Myxococcus xanthus with non‐motile, antibiotic producer Streptomyces coelicolor was examined using a variety experimental approaches. cells prey on S. , forming streams ordered that lyse hyphae in contact area between two colonies. The interaction increases actinorhodin production by up to 20‐fold and triggers aerial mycelium production. Other bacteria are also able induce these processes though lesser extent. These studies offer new clues...
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 present article describes the isolation of a new natural product lobophorin family, designated as K (1), from cultures marine actinobacteria Streptomyces sp. M-207, previously isolated cold-water coral Lophelia pertusa collected at 1800 m depth during an expedition to submarine Avilés Canyon. Its structure was determined using combination spectroscopic techniques, mainly ESI-TOF MS and 1D 2D NMR. This displayed cytotoxic activity against two human tumor cell lines, such pancreatic...
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...
ABSTRACT The biosynthetic gene cluster for the aromatic polyketide steffimycin of anthracycline family has been cloned and characterized from “ Streptomyces steffisburgensis ” NRRL 3193. Sequence analysis a 42.8-kbp DNA region revealed presence 36 open reading frames (ORFs) (one them incomplete), 24 which, spanning 26.5 kb, are probably involved in biosynthesis. They code all activities required biosynthesis, tailoring, regulation, resistance but show no evidence genes l -rhamnose...
Cellophane cultivation techniques have been proven to be useful for the study of colony growth in Streptomyces. Results obtained by this procedure indicate that, S. antibioticus, substrate mycelium was a nutrient support aerial growth. Oleandomycin synthesis starts before formation and may play an important role during
Abstract Streptomyces sp. Tü 6176 produces the cytotoxic benzoxazole nataxazole. Bioinformatic analysis of genome this organism predicts presence 38 putative secondary‐metabolite biosynthesis gene clusters, including those involved in AJI9561 and its derivative nataxazole, antibiotic hygromycin B, ionophores enterobactin coelibactin. The nataxazole cluster was identified characterized: it lacks O‐methyltransferase required to convert into This activity might act as a resistance mechanism,...
The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G (1), with strong antibiotic activity against several clinically relevant resistant pathogens are described herein. This natural product was obtained from cultures the marine actinomycete Streptomyces althioticus MSM3, isolated samples intertidal seaweed Ulva sp. collected in Cantabrian Sea (Northeast Atlantic Ocean). Particularly interesting is its Mycobacterium tuberculosis clinical...
ABSTRACT A 9.8-kb DNA region from the oleandomycin gene cluster in Streptomyces antibioticus was cloned. Sequence analysis revealed presence of 8 open reading frames encoding different enzyme activities involved biosynthesis one two 2,6-deoxysugars attached to aglycone: l -oleandrose (the oleW , oleV oleL and oleU genes) d -desosamine oleNI oleT genes), or both oleS oleE genes). albus strain harboring oleG2 glycosyltransferase integrated into chromosome constructed. This transformed with...