A5006946571- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Plant-Microbe Interactions and Immunity
- Fungal Biology and Applications
- Bacterial Genetics and Biotechnology
- Plant Disease Resistance and Genetics
- Plant biochemistry and biosynthesis
- Synthetic Organic Chemistry Methods
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- Pharmacogenetics and Drug Metabolism
- Steroid Chemistry and Biochemistry
- Enzyme Structure and Function
- Peptidase Inhibition and Analysis
- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- Phytochemical compounds biological activities
- Enzyme Catalysis and Immobilization
- Antibiotic Resistance in Bacteria
- Carbohydrate Chemistry and Synthesis
- DNA and Nucleic Acid Chemistry
- Microbial Metabolites in Food Biotechnology
- Antifungal resistance and susceptibility
- Toxin Mechanisms and Immunotoxins
- Mycobacterium research and diagnosis
Universidad de León
2010-2022
Instituto de Biotecnología de León
2004-2014
Czech Academy of Sciences, Institute of Biotechnology
2002-2004
Universidad de Oviedo
1988-1996
University of Cambridge
1993-1996
Hokkaido University
1992
The macrocyclic polyketides rapamycin and FK506 are potent immunosuppressants that prevent T-cell proliferation through specific binding to intracellular protein receptors (immunophilins). cloning alteration of the biosynthetic genes for these might allow biosynthesis clinically valuable analogues. We report here three clustered polyketide synthase responsible in Streptomyces hygroscopicus together encode 14 homologous sets enzyme activities (modules), each catalyzing a round chain...
The amino acid sequences of a large number polyketide synthase domains that catalyse the transacylation either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which acyltransferase diverged according to whether they specific for methylmalonyl-CoA. These differences are sufficiently clear allow unambiguous assignment newly-sequenced modular synthases. Comparison with recently-determined structure malonyltransferase from...
During assembly of complex polyketide antibiotics like erythromycin A, molecular recognition by the multienzyme synthase controls stereochemical outcome as each successive methylmalonyl-coenzyme A (CoA) extender unit is added. Acylation purified erythromycin-producing has shown that all six acyltransferase domains have identical stereospecificity for their normal substrate, (2 S )-methylmalonyl-CoA. In contrast, configuration methyl-branched centers in product, are derived from...
The biosynthetic gene cluster for the 26-membered ring of polyene macrolide pimaricin extends about 110 kilobase pairs contiguous DNA in genome Streptomyces natalensis. Two sets polyketide synthase (PKS) genes are separated by a group small polyketide-functionalizing genes. genes, pimS0 and pimS1, have been fully sequenced disrupted proving involvement each these biosynthesis. encodes relatively acetate-activating PKS (∼193 kDa) that appears to work as loading protein which "presents"...
A chemically novel autoinducer (PI factor) has been purified from cultures of the pimaricin producer Streptomyces natalensis ATCC27448. The chemical structure PI molecule was identified as 2,3-diamino-2,3-bis (hydroxymethyl)-1,4-butanediol. Pimaricin biosynthesis in S. npi287, a mutant impaired production, restored by supplementation with either A-factor griseus IFO13350 or factor. did not synthesize A-factor. active at very low concentrations (50–350 nm). threshold level 50 nm required to...
The domain structure of the 6-deoxyerythronolide B synthase 1 component erythromycin-producing polyketide from Saccharopolyspora erythraea has been investigated using limited proteolysis and active-site labeling. Trypsin, elastase, endoproteinase Glu-C, Arg-C were used to cleave multienzyme, sizes resulting fragments assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. location within primary was established N-terminal sequence analysis. cleavage pattern followed boundaries...
Sequencing of the DNA region on left fringe pimaricin gene cluster revealed presence a 3.6-kb gene, pimR, whose deduced product (1,198 amino acid residues) was found to have sequence homology with bacterial regulatory proteins. Database comparisons that PimR represents archetype new class regulators, combining Streptomyces antibiotic protein (SARP)-like N-terminal section C-terminal half homologous guanylate cyclases and large ATP-binding regulators LuxR family. Gene replacement pimR from...
Sequencing of the DNA region on left fringe pimaricin gene cluster revealed presence a 579 bp gene, pimM, whose deduced product (192 aa) was found to have amino acid sequence homology with bacterial regulatory proteins. Database comparisons that PimM combines an N-terminal PAS domain C-terminal helix–turn–helix (HTH) motif LuxR type. Gene replacement pimM from Streptomyces natalensis chromosome mutant version lacking HTH DNA-binding resulted in complete loss production, suggesting is...
The macrocyclic polyketide tacrolimus (FK506) is a potent immunosuppressant that prevents T-cell proliferation produced solely by Streptomyces species. We report here the first draft genome sequence of true FK506 producer, tsukubaensis NRRL 18488, tacrolimus-producing strain was isolated and contains full biosynthesis gene cluster.
Hydroxylation of C-12 is one the final steps in biosynthesis erythromycin A (ErA). point uncertainty pathway has been whether hydroxylase operates on each two possible substrates, B (ErB) and D (ErD). Stassi et al. have cloned gene, designated eryK, which encodes P-450 monooxygenase responsible for hydroxylation Saccharopolyspora erythraea [Stassi, D., Donadio, S., Staver, M. J., & Katz, L. (1993) J. Bacteriol. 175, 182-189]. We report overproduction EryK Escherichia coli as insoluble...
We have produced a panel of monoclonal antibodies to pneumolysin, the membrane-damaging toxin from Streptococcus pneumoniae. used these identify three regions sequence that are involved in lytic mechanism this toxin. Two sites probably form cell binding site Antibodies third inhibit action but not cells. This is engaged oligomerization process formation pores membranes. epitopes also present related perfringolysin O.