A5040048441- Plant biochemistry and biosynthesis
- Microbial Natural Products and Biosynthesis
- Chronic Lymphocytic Leukemia Research
- Essential Oils and Antimicrobial Activity
- Microbial Metabolic Engineering and Bioproduction
- Lymphoma Diagnosis and Treatment
- Biochemical and biochemical processes
- Natural product bioactivities and synthesis
- Bacterial Genetics and Biotechnology
- Plant Gene Expression Analysis
- Immunodeficiency and Autoimmune Disorders
- Traditional Chinese Medicine Analysis
- Galectins and Cancer Biology
- Fungal and yeast genetics research
- Photosynthetic Processes and Mechanisms
- Peptidase Inhibition and Analysis
- Toxin Mechanisms and Immunotoxins
- Urinary and Genital Oncology Studies
- Genomics, phytochemicals, and oxidative stress
- Redox biology and oxidative stress
- Monoclonal and Polyclonal Antibodies Research
- T-cell and Retrovirus Studies
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Edible Oils Quality and Analysis
Centre for Research and Technology Hellas
2015-2024
Western General Hospital
2024
Mediterranean Agronomic Institute of Chania
2000-2013
Universitätsklinikum Aachen
2007-2008
Sidney Kimmel Cancer Center
2001
Thomas Jefferson University
1999-2001
Fox Chase Cancer Center
1992-1997
Molecular Oncology (United States)
1992
Pasteur Hellenic Institute
1991
Monoterpenes have an established use in the food and cosmetic industries recently also found application as advanced biofuels. Although metabolic engineering efforts so far achieved significant yields of larger terpenes, monoterpene productivity is lagging behind. Here, we set out to establish a monoterpene-specific production platform Saccharomyces cerevisiae identified sequential reaction mechanism yeast farnesyl diphosphate synthase Erg20p be important factor limiting yield. To overcome...
The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors plants we transformed cells expressing with a tomato cDNA library selected for surviving after the induction Bax. This genetic screen allows identification genes, which inhibit either directly or indirectly phenotype Using this method number clones were isolated, more potent encodes protein homologous to class θ glutathioneS-transferases. Bax-inhibiting (BI) was...
Terpene synthases are responsible for the biosynthesis of complex chemical defense arsenal plants and microorganisms. How do these enzymes, which all appear to share a common terpene synthase fold, specify many different products made almost entirely from one only three substrates? Elucidation structure 1,8-cineole Salvia fruticosa (Sf-CinS1) combined with analysis functional phylogenetic relationships enzymes within species identified active-site residues product specificity. Thus, Sf-CinS1...
Abstract Background Terpenoids constitute a large family of natural products, attracting commercial interest for variety uses as flavours, fragrances, drugs and alternative fuels. Saccharomyces cerevisiae offers versatile cell factory, the precursors terpenoid biosynthesis are naturally synthesized by sterol biosynthetic pathway. Results S. wild type yeast cells, selected their capacity to produce high levels were targeted improvement aiming increase production. Recyclable integration...
Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial "chassis" have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, potential such production systems facilitate elucidation has been underexplored. Here we report on application a modular terpene platform characterization pathway leading potent antioxidant carnosic acid and related diterpenes Salvia...
Abstract Synthetic biology efforts for the production of valuable chemicals are frequently hindered by structure and regulation native metabolic pathways chassis. This is particularly evident in case monoterpenoid Saccharomyces cerevisiae , where canonical terpene precursor geranyl diphosphate tightly coupled to biosynthesis isoprenoid compounds essential yeast viability. Here, we establish a synthetic orthogonal pathway based on an alternative precursor, neryl diphosphate. We identify...
Taxol is a potent drug used in various cancer treatments. Its complex structure has prompted extensive research into its biosynthesis. However, certain critical steps, such as the formation of oxetane ring, which essential for activity, have remained unclear. Previous proposals suggested that follows acetylation taxadien-5α-ol. Here, we proposed ring formed by cytochrome P450-mediated oxidation events occur prior to C5 acetylation. To test this hypothesis, analyzed genomic and transcriptomic...
The Tpl-2 locus, cloned by provirus tagging from one of three sublines the Moloney leukemia virus-induced rat thymoma 2769, defines a gene encoding protein kinase associated with progression in 22.5% tumors. is expressed primarily spleen, thymus, liver, and lung. Provirus integration occurs last intron gene, leading to expression truncated mRNA that terminates proviral long terminal repeat encodes an altered C-terminal domain. Strong evidence this genetic change confers growth advantage...
The cytoplasmic serine-threonine protein kinase coded for by the c-akt proto-oncogene features a C-like catalytic domain and unique NH2-terminal (AH domain). AH is member of superfamily whose prototype was observed in pleckstrin (pleckstrin homology, or PH, In this communication, we present evidence that AH/PH protein-protein interaction which mediates formation Akt complexes. between domains highly specific, as determined failure to bind AKT2. domain-mediated interactions depend on...
Provirus insertion in the last intron of Tpl-2 gene retrovirus-induced rat T-cell lymphomas results enhanced expression a carboxy-terminally truncated kinase. Here we show that protein exhibits an approximately sevenfold higher catalytic activity and is two- to threefold more efficient activating MAPK SAPK pathways relative wild-type protein. The GST fusion carboxy-terminal tail interact when coexpressed Sf9 cells. Their interaction down-regulates kinase suggesting tail-directed...
The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, phenotype associated with oxidative stress and disruption mitochondrial functions. Screening tomato two-hybrid library for interacting proteins five homologous Tau class GSTs, which readily form heterodimers between them BI-GST. All six LeGSTUs were found to be able protect yeast cells from prooxidant-induced cell death. efficiency each LeGSTU was prooxidant-specific, indicating...
Mitogenic signals initiated at the plasma membrane by extracellular factors acting on receptor tyrosine kinases or G protein-coupled receptors are transmitted to nucleus through an intricate signaling network. Components of this network participate, upon stimulation, in a complex array phosphorylation-dependent protein-protein interactions which leads formation transient multimolecular complexes. Complexes containing products protooncogenes ras and raf-1 protein kinase MEK-1 activate...
Terpenes are a large class of natural products, many which used in cosmetics, pharmaceuticals, or biofuels. However, terpene's industrial application is frequently hindered by limited availability sources low yields chemical synthesis. In this report, we developed modular platform based on standardized and exchangeable parts to reproduce potentially expand the diversity terpene structures Saccharomyces cerevisiae. By combining different module-specific parts, exploited substrate promiscuity...
Carnosic acid (CA) is a phenolic diterpene with anti-tumour, anti-diabetic, antibacterial and neuroprotective properties that produced by number of species from several genera the Lamiaceae family, including Salvia fruticosa (Cretan sage) Rosmarinus officinalis (Rosemary). To elucidate CA biosynthesis, glandular trichome transcriptome data S. were mined for terpene synthase genes. Two putative genes, namely SfCPS SfKSL, showing similarities to copalyl diphosphate kaurene synthase-like...
Terpenoids (isoprenoids) have numerous applications in flavors, fragrances, drugs and biofuels. The number of microbially produced terpenoids is increasing as new biosynthetic pathways are being elucidated. However, efforts to improve terpenoid production yeast mostly taken advantage existing knowledge the sterol pathway, while many additional factors may affect output engineered system.Aiming develop a strain that can support high titers sclareol, diterpene great importance for perfume...
Various plant factors are co-opted by virus elements (RNA, proteins) and have been shown to act in pathways affecting accumulation defence. Here, an interaction between Pepino mosaic (PepMV) triple gene block protein 1 (TGBp1; p26) tomato catalase (CAT1), a crucial enzyme the decomposition of toxic hydrogen peroxide (H₂O₂), was identified using yeast two-hybrid assay, confirmed via vitro pull-down assay bimolecular fluorescent complementation (BiFC) planta. Each independently localized...
Salvia diterpenes have been found to health promoting properties. Among them, carnosic acid and carnosol, tanshinones sclareol are well known for their cardiovascular, antitumor, antiinflammatory antioxidant activities. However, many of these compounds not available at a constant supply developing biotechnological methods production could provide sustainable alternative. The transcriptome S.pomifera glandular trichomes was analysed aiming identify genes that be used in the engineering...
Yarrowia lipolytica is a well-studied oleaginous yeast known for its ability to accumulate and store intracellular lipids, while growing on diverse, non-conventional substrates. Amongst them, crude glycerol, low-cost by-product of the biodiesel industry, appears be an interesting option scaling up sustainable single-cell oil production process. Adaptive laboratory evolution (ALE) powerful tool force metabolic adaptations endowing tolerance stressful environmental conditions, generating...
Spontaneous mutants of Pseudomonas aeruginosa selected by ciprofloxacin were studied for outer membrane alterations. Acquisition resistance was at least partially related to defects in lipopolysaccharide synthesis. When combined with beta-lactams and aminoglycosides, several alterations proteins noted.
The in vitro binding of four Helicobacter pylori strains to human gastric mucin was studied with an enzyme-linked immunosorbent assay. All were found bind purified mucin. Neuraminidase treatment and nonspecific oxidation decreased bacterial adherence the macromolecule. Mucin preparations also inhibit attachment H. HEp-2 monolayers.
In a genetic screen to identify modifiers of Bax-dependent lethality in yeast, the C terminus OYE2 was isolated based on its capacity restore sensitivity Bax-resistant yeast mutant strain. Overexpression full-length suppresses Bax lowers endogenous reactive oxygen species (ROS), increases resistance H2O2-induced programmed cell death (PCD), and significantly ROS levels generated by organic prooxidants. Reciprocally, Δoye2 strains are sensitive prooxidant-induced PCD. knock-out analysis...