A5044079805- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Microbial Metabolism and Applications
- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- Microbial Metabolic Engineering and Bioproduction
- Synthetic Organic Chemistry Methods
- Cancer therapeutics and mechanisms
- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- Microbial Metabolites in Food Biotechnology
- Probiotics and Fermented Foods
- Plant-Microbe Interactions and Immunity
- Bioactive Compounds and Antitumor Agents
- Enzyme Production and Characterization
- Plant Disease Resistance and Genetics
- Chemical Synthesis and Analysis
- Mycotoxins in Agriculture and Food
- Phytochemical compounds biological activities
- Hearing, Cochlea, Tinnitus, Genetics
- Gut microbiota and health
- Enzyme Catalysis and Immobilization
- Fungal Biology and Applications
- Phytochemistry and biological activity of medicinal plants
- Pharmaceutical and Antibiotic Environmental Impacts
University of Ljubljana
2016-2025
Explora (Italy)
2022
Acies Bio (Slovenia)
2010-2019
Instituto de Biomedicina y Biotecnología de Cantabria
2013-2015
Universidad de Cantabria
2013-2015
Helmholtz Institute for Pharmaceutical Research Saarland
2015
Helmholtz Centre for Infection Research
2015
Saarland University
2015
St. Jude Children's Research Hospital
2006
Hadassah Medical Center
2002
The surprising discovery has been made that the gene product RapK is required for production of starter unit in rapamycin polyketide cluster. It shown a deletion mutant (Streptomyces hygroscopicus MG2–10) provides clean background mutasynthesis pre-rapamycin (the precursor to rapamycin, see structure) when fed with novel units. Supporting information this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z462784_s.pdf or from author. Please note: publisher not...
ABSTRACT Rapamycin is an important macrocyclic polyketide produced by Streptomyces hygroscopicus and showing immunosuppressive, antifungal, antitumor activities as well displaying anti-inflammatory neuroregenerative properties. The immense pharmacological potential of rapamycin has led to the production array analogues, including through genetic engineering biosynthetic gene cluster. This cluster contains several putative regulatory genes. Based on DNA sequence analysis, products genes rapH...
FK506 (tacrolimus) is a secondary metabolite with potent immunosuppressive activity, currently registered for use as immunosuppressant after organ transplantation. and FK520 are biogenetically related natural products that synthesized by combined polyketide synthase/nonribosomal peptide synthetase systems. The entire gene cluster biosynthesis of from Streptomyces hygroscopicus var. ascomyceticus has been cloned sequenced. On the other hand, sp. MA6548 (ATCC55098) was sequenced only...
Antimicrobial resistance and the shortage of novel antibiotics have led to an urgent need for new antibacterial drug leads. Several existing natural product scaffolds (including chelocardins) not been developed because their suboptimal pharmacological properties could be addressed at time. It is demonstrated here that reviving such compounds through application biosynthetic engineering can deliver candidates. Through a rational approach, carboxamido moiety tetracyclines (an important...
Spread of antimicrobial resistance and shortage novel antibiotics have led to an urgent need for new antibacterials. Although aminoglycoside (AGs) are very potent anti-infectives, their use is largely restricted due serious side-effects, mainly nephrotoxicity ototoxicity. We evaluated the ototoxicity various AGs selected from a larger set on basis strong antibacterial activities against multidrug-resistant clinical isolates ESKAPE panel: gentamicin, gentamicin C1a, apramycin, paromomycin...
New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of bottlenecks is elucidation targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for rapid classification compounds into those with precedented unprecedented modes action. We established response library Bacillus subtilis covering 91 comparator compounds, mathematical was developed aid data analysis. Comparison responses (CoPR) allows...
Abstract Background FK506 (Tacrolimus) is an important immunosuppressant, produced by industrial biosynthetic processes using various Streptomyces species. Considering the complex structure of FK506, it reasonable to expect regulatory networks controlling its biosynthesis. Regulatory elements, present in gene clusters can have a profound influence on final yield target product and play role development bioprocesses. Results Three putative namely fkbR , belonging LysR-type family, fkbN large...
Lincomycin A is a clinically important antimicrobial agent produced by Streptomyces lincolnensis. In this study, new regulator designated LmbU (GenBank accession no. ABX00623.1) was identified and characterized to regulate lincomycin biosynthesis in S. lincolnensis wild-type strain NRRL 2936. Both inactivation overexpression of lmbU resulted significant influences on production. Transcriptional analysis vivo neomycin resistance (Neor) reporter assays demonstrated that activates expression...
Streptomyces rapamycinicus strain NRRL 5491 produces the important drug rapamycin. It has a large genome of 12.7 Mb, which over 3 Mb consists 48 secondary metabolite biosynthesis clusters.
To combat the increasing spread of antimicrobial resistance and shortage novel anti-infectives, one strategy for development new antibiotics is to optimize known chemical scaffolds. Here, we focus on biosynthetic engineering Amycolatopsis sulphurea derivatization atypical tetracycline chelocardin its potent broad-spectrum derivative 2-carboxamido-2-deacetyl-chelocardin. Heterologous genes were introduced into this producer modify functional groups generate derivatives. We demonstrate...
ABSTRACT Most biosynthetic gene clusters (BGC) encoding the synthesis of important microbial secondary metabolites, such as antibiotics, are either silent or poorly expressed; therefore, to ensure a strong pipeline novel there is need develop rapid and efficient strain development approaches. This study uses comparative genome analysis instruct rational improvement, using Streptomyces rimosus , producer antibiotic oxytetracycline (OTC) model system. Sequencing genomes two industrial strains...
The production of epothilone mixtures is a direct consequence the substrate tolerance module 3 acyltransferase (AT) domain polyketide synthase (PKS) which utilises both malonyl- and methylmalonyl-CoA extender units. Particular amino acid motifs in active site AT domains influence selection for (YASH) or malonyl-CoA (HAFH). This motif appears hybrid form (HASH) epoAT3 may represent molecular basis relaxed specificity domain. To investigate this possibility from modules 2 PKS were examined...
Two new Lactobacillus plantarum strains, KR6-DSM 28780 and M5 isolated from sour turnip traditional dried fresh cheese, respectively, were evaluated for species identity, antibiotic susceptibility, resistance to gastrointestinal conditions adaptive response low pH. Resistance mechanisms involved in the adaptation acid-induced stress these two strains investigated by quantitative PCR of atpA, cfa1, mleS hisD genes. In addition absence resistance, L. showed excellent survival rates at pH...
ABSTRACT We report the draft genome of Streptomyces rimosus (ATCC 10970), a soil isolate that produces oxytetracycline, commercially important and clinically useful antibiotic.
The medically important immunosuppressant FK506 is a structurally complex macrolactone biosynthesized by combined polyketide synthase and nonribosomal peptide synthetase enzyme complex. Its acyltransferase domain 4 (AT4) selects an unusual extender unit, resulting in allyl moiety on carbon 21 of the backbone. Based AT4 domain, chemobiosynthetic processes have been developed that enable introduction diverse moieties at position. However, novel were introduced into backbone are chemically...
The function of gene products involved in the biosynthesis clinically important polyketide rapamycin were elucidated by biotransformation and complementation
Tetracyclines (TCs) are medically important antibiotics from the polyketide family of natural products. Chelocardin (CHD), produced by Amycolatopsis sulphurea, is a broad-spectrum tetracyclic antibiotic with potent bacteriolytic activity against number Gram-positive and Gram-negative multi-resistant pathogens. CHD has an unknown mode action that different TCs. It some structural features define it as 'atypical' and, notably, active tetracycline-resistant Identification characterization...