Ecdysteroids (ECs) are steroid hormones originally found in the animal kingdom where they function as insect molting hormones. Interestingly, a relatively high number of these substances can also be formed in plant cells. Moreover, ECs have certain regulatory effects on plant physiology, but their role in plants still requires further study. One of the main aims of the present study was to verify a hypothesis that fenarimol, an inhibitor of the biosynthesis of ECs in the animal kingdom, also affects the content of endogenous ECs in plants using winter wheat Triticum aestivum L. as a model plant. The levels of endogenous ECs in winter wheat, including the estimation of their changes during a course of different temperature treatments, have been determined using a sensitive analytical method based on UHPLC-MS/MS. Under our experimental conditions, four substances of EC character were detected in the tissue of interest in amounts ranging from less than 1 to over 200 pg·g-1 FW: 20-hydroxyecdysone, polypodine B, turkesterone, and isovitexirone. Among them, turkesterone was observed to be the most abundant EC and accumulated mainly in the crowns and leaves of wheat. Importantly, the level of ECs was observed to be dependent on the age of the plants, as well as on growth conditions (especially temperature). Fenarimol, an inhibitor of a cytochrome P450 monooxygenase, was shown to significantly decrease the level of naturally occurring ECs in experimental plants, which may indicate its potential use in studies related to the biosynthesis and physiological function of these substances in plants.
- MeSH
- biologické přípravky chemie metabolismus MeSH
- chromatografie kapalinová metody MeSH
- ekdysteroidy biosyntéza chemie MeSH
- listy rostlin účinky léků metabolismus MeSH
- molekulární struktura MeSH
- průmyslové fungicidy farmakologie MeSH
- pšenice růst a vývoj metabolismus MeSH
- pyrimidiny farmakologie MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
Calanolides are tetracyclic 4-substituted dipyranocoumarins. Calanolide A, isolated from the leaves and twigs of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens, is the first member of this group of compounds with anti-HIV-1 activity mediated by reverse transcriptase inhibition. Calanolides are classified pharmacologically as non-nucleoside reverse transcriptase inhibitors (NNRTI). There are at least 15 naturally occurring calanolides distributed mainly within the genus Calophyllum, but some of them are also present in the genus Clausena. Besides significant anti-HIV properties, which have been exploited towards potential development of new NNRTIs for anti-HIV therapy, calanolides have also been found to possess anticancer, antimicrobial and antiparasitic potential. This review article provides a comprehensive update on all aspects of naturally occurring calanolides, including their chemistry, natural occurrence, biosynthesis, pharmacological and toxicological aspects including mechanism of action and structure activity relationships, pharmacokinetics, therapeutic potentials and available patents.
- MeSH
- biologické přípravky chemie metabolismus farmakologie terapeutické užití MeSH
- lidé MeSH
- pyranokumariny chemie metabolismus farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- biologická terapie škodlivé účinky MeSH
- biologické přípravky metabolismus škodlivé účinky terapeutické užití MeSH
- fertilita účinky léků MeSH
- kojení MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- matka - expozice noxám MeSH
- psoriáza * imunologie patologie terapie MeSH
- těhotenství * účinky léků MeSH
- vývoj plodu účinky léků MeSH
- Check Tag
- lidé MeSH
- těhotenství * účinky léků MeSH
- ženské pohlaví MeSH
In this work we present the third generation of FAst MEtabolizer (FAME 3), a collection of extra trees classifiers for the prediction of sites of metabolism (SoMs) in small molecules such as drugs, druglike compounds, natural products, agrochemicals, and cosmetics. FAME 3 was derived from the MetaQSAR database ( Pedretti et al. J. Med. Chem. 2018 , 61 , 1019 ), a recently published data resource on xenobiotic metabolism that contains more than 2100 substrates annotated with more than 6300 experimentally confirmed SoMs related to redox reactions, hydrolysis and other nonredox reactions, and conjugation reactions. In tests with holdout data, FAME 3 models reached competitive performance, with Matthews correlation coefficients (MCCs) ranging from 0.50 for a global model covering phase 1 and phase 2 metabolism, to 0.75 for a focused model for phase 2 metabolism. A model focused on cytochrome P450 metabolism yielded an MCC of 0.57. Results from case studies with several synthetic compounds, natural products, and natural product derivatives demonstrate the agreement between model predictions and literature data even for molecules with structural patterns clearly distinct from those present in the training data. The applicability domains of the individual models were estimated by a new, atom-based distance measure (FAMEscore) that is based on a nearest-neighbor search in the space of atom environments. FAME 3 is available via a public web service at https://nerdd.zbh.uni-hamburg.de/ and as a self-contained Java software package, free for academic and noncommercial research.
Plant secondary metabolism evolved in the context of highly organized and differentiated cells and tissues, featuring massive chemical complexity operating under tight environmental, developmental and genetic control. Biotechnological demand for natural products has been continuously increasing because of their significant value and new applications, mainly as pharmaceuticals. Aseptic production systems of plant secondary metabolites have improved considerably, constituting an attractive tool for increased, stable and large-scale supply of valuable molecules. Surprisingly, to date, only a few examples including taxol, shikonin, berberine and artemisinin have emerged as success cases of commercial production using this strategy. The present review focuses on the main characteristics of plant specialized metabolism and their implications for current strategies used to produce secondary compounds in axenic cultivation systems. The search for consonance between plant secondary metabolism unique features and various in vitro culture systems, including cell, tissue, organ, and engineered cultures, as well as heterologous expression in microbial platforms, is discussed. Data to date strongly suggest that attaining full potential of these biotechnology production strategies requires being able to take advantage of plant specialized metabolism singularities for improved target molecule yields and for bypassing inherent difficulties in its rational manipulation.
- MeSH
- artemisininy izolace a purifikace metabolismus MeSH
- axenická kultura MeSH
- berberin izolace a purifikace metabolismus MeSH
- biologické přípravky izolace a purifikace metabolismus MeSH
- biotechnologie metody MeSH
- buněčné kultury MeSH
- fytonutrienty biosyntéza izolace a purifikace MeSH
- metabolické inženýrství metody MeSH
- naftochinony izolace a purifikace metabolismus MeSH
- paclitaxel biosyntéza izolace a purifikace MeSH
- rostlinné buňky chemie metabolismus MeSH
- rostliny chemie genetika metabolismus MeSH
- sekundární metabolismus MeSH
- techniky tkáňových kultur MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Covering: up to 2017This review covers the biosynthetic and evolutionary aspects of lincosamide antibiotics, antitumour pyrrolobenzodiazepines (PBDs) and the quorum-sensing molecule hormaomycin. These structurally and functionally diverse groups of complex natural products all incorporate rarely occurring 4-alkyl-l-proline derivatives (APDs) biosynthesized from l-tyrosine through an unusual specialized pathway catalysed by a common set of six proteins named Apd1-Apd6. We give an overview of APD formation, which involves unusual enzyme activities, and its incorporation, which is based either on nonribosomal peptide synthetase (PBDs, hormaomycin) or a unique hybrid ergothioneine-dependent condensation system followed by mycothiol-dependent sulphur atom incorporation (lincosamides). Furthermore, within the public databases, we identified 36 novel unannotated biosynthetic gene clusters that putatively encode the biosynthesis of APD compounds. Their products presumably include novel PBDs, but also novel classes of APD compounds, indicating an unprecedented potential for the diversity enhancement of these functionally versatile complex metabolites. In addition, phylogenetic analysis of known and novel gene clusters for the biosynthesis of APD compounds allowed us to infer novel evolutionary hypotheses: Apd3 methyltransferase originates from a duplication event in a hormaomycin biosynthetic gene cluster ancestor, while putative Apd5 isomerase is evolutionarily linked to PhzF protein from the biosynthesis of phenazines. Lastly, we summarize the achievements in preparing hybrid APD compounds by directing their biosynthesis, and we propose that the number of nature-like APD compounds could by multiplied by replacing l-proline residues in various groups of complex metabolites with APD, i.e. by imitating the natural process that occurs with lincosamides and PBDs, in which the replacement of l-proline for APD has proved to be an evolutionary successful concept.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- benzodiazepiny chemie farmakologie MeSH
- biologické přípravky chemie metabolismus farmakologie MeSH
- cystein metabolismus MeSH
- depsipeptidy chemie metabolismus farmakologie MeSH
- ergothionein metabolismus MeSH
- glykopeptidy metabolismus MeSH
- inositol metabolismus MeSH
- lidé MeSH
- linkomycin chemie farmakologie MeSH
- linkosamidy biosyntéza farmakologie MeSH
- molekulární evoluce * MeSH
- molekulární struktura MeSH
- protinádorové látky chemie metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below.
- MeSH
- akutní poškození plic chemicky indukované metabolismus MeSH
- biologické přípravky antagonisté a inhibitory metabolismus MeSH
- fosfolipidy antagonisté a inhibitory metabolismus MeSH
- lidé MeSH
- lipopolysacharidy metabolismus toxicita MeSH
- plíce účinky léků metabolismus MeSH
- plicní surfaktanty antagonisté a inhibitory metabolismus MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Anticancer pyrrolobenzodiazepines (PBDs) are one of several groups of natural products that contain unusual 4-alkyl-l-proline derivatives (APDs) in their structure. APD moieties of PBDs are characterized by high structural diversity achieved through unknown biosynthetic machinery. Based on LC-MS analysis of culture broths, feeding experiments, and protein assays, we show that APDs are not incorporated into PBDs in their final form as was previously hypothesized. Instead, a uniform building block, 4-propylidene-l-proline or 4-ethylidene-l-proline, enters the condensation reaction. The subsequent postcondensation steps are initiated by the introduction of an additional double bond catalyzed by a FAD-dependent oxidoreductase, which we demonstrated with Orf7 from anthramycin biosynthesis. The resulting double bond arrangement presumably represents a prerequisite for further modifications of the APD moieties. Our study gives general insight into the diversification of APD moieties of natural PBDs and provides proof-of-principle for precursor directed and combinatorial biosynthesis of new PBD-based antitumor compounds.
Recently, a growing number of plant essential oils (EOs) have been tested against a wide range of arthropod pests with promising results. EOs showed high effectiveness, multiple mechanisms of action, low toxicity on non-target vertebrates and potential for the use of byproducts as reducing and stabilizing agents for the synthesis of nanopesticides. However, the number of commercial biopesticides based on EOs remains low. We analyze the main strengths and weaknesses arising from the use of EO-based biopesticides. Key challenges for future research include: (i) development of efficient stabilization processes (e.g., microencapsulation); (ii) simplification of the complex and costly biopesticide authorization requirements; and (iii) optimization of plant growing conditions and extraction processes leading to EOs of homogeneous chemical composition.
It is demonstrated that numerous bacteria are able to attach to surfaces of equipment used for food handling or processing. In this study, a strain of Enterococcus durans, originally isolated from a milking machine surface, was firstly studied for its biofilm formation potential on plastic and stainless steel supports. The strain was found to be a biofilm producer either at 25, 30 or 37 °C on polystyrene microtitre plates, with a best adherence level observed at 25 °C. En. durans showed a strong adhesion to stainless steel AISI-304. Antibacterial and anti-adherence activities of En. durans were tested against four foodborne pathogens (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853 and Listeria innocua CLIP 74915) which were shown as biofilm producers on both plastic and stainless steel. En. durans cells and cell-free culture supernatant showed a significant (P < 0.05) inhibition potential of the pathogens either on solid media or in broth co-cultures. Characterization of the antibacterial substances indicated their proteinaceous nature which assigned them most probably to bacteriocins group.
- MeSH
- bakteriální adheze účinky léků MeSH
- bakteriální proteiny metabolismus MeSH
- biofilmy účinky léků MeSH
- biologické přípravky metabolismus MeSH
- Enterococcus metabolismus fyziologie MeSH
- gramnegativní bakterie účinky léků fyziologie MeSH
- grampozitivní bakterie účinky léků fyziologie MeSH
- mikrobiologie životního prostředí * MeSH
- nerezavějící ocel MeSH
- plastické hmoty MeSH
- potravinářská mikrobiologie MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
