Novel Selectable Marker Sesquiterpenoid Antibiotic Pentalenolactone.

Antibiotic resistance has been and remains a major problem in our society. The main solution to this problem is to search and study the mechanisms of antibiotic action. Many groups of secondary metabolites, including antimicrobial ones, are produced by the phylum.

The Protein Engineering of Zearalenone Hydrolase Results in a Shift in the pH Optimum of the Relative Activity of the Enzyme.

An acidic shift in the pH profile of zearalenone hydrolase (ZHD), the most effective and well-studied zearalenone-specific lactone hydrolase, is required to extend the range of applications for the enzyme as a decontamination agent in the feed and food production industries. Amino acid substitutions were engineered in the active center of the enzyme to decrease the pKa values of the catalytic residues E126 and H242. The T216K substitution provided a shift in the pH optimum by one unit to the acidic region, accompanied by a notable expansion in the pH profile under acidic conditions.

Conformational dynamics of the enzyme-substrate complex of protein kinase A with pseudosubstrate SP20 and adenosine triphosphate.

The phosphorylation reaction, catalyzed by the enzyme protein kinase A (PKA), plays one of the key roles in the work of the glutamatergic system, primarily involved in memory functioning. The analysis of the dynamic behavior of the enzyme-substrate complex allows one to learn the mechanism of the enzymatic reaction. According to the results of classical molecular dynamics calculations followed by hierarchical clustering, the most preferred proton acceptor during the phosphorylation reaction catalyzed by PKA is the carboxyl group of the amino acid residue Asp166; however, the γ-phosphate group of ATP can also act as an acceptor.

Matrikines of Sea Cucumbers: Structure, Biological Activity and Mechanisms of Action.

Matrikines (MKs), the products of enzymatic fragmentation of various extracellular matrix (ECM) proteins, regulate cellular activity by interacting with specific receptors. MKs affect cell growth, proliferation, and migration, can induce apoptosis and autophagy, and are also effectively used in biomedicine and functional nutrition. Recently, there has been great interest in the structural features and biological activity of MKs from various sources.

Human DNA from the oldest Eneolithic cemetery in Nalchik points the spread of farming from the Caucasus to the Eastern European steppes.

The Darkveti-Meshoko culture (c.5000-3500/3300 BCE) is the earliest known farming community in the Northern Caucasus, but its contribution to the genetic profile of the neighboring steppe herders has remained unclear. We present analysis of human DNA from the Nalchik cemetery-the oldest Eneolithic site in the Northern Caucasus-which shows a link with the LowerVolga's first herders of the Khvalynsk culture.

A systematic overview of strategies for photosensitizer and light delivery in antibacterial photodynamic therapy for lung infections.

Antimicrobial photodynamic therapy (aPDT) emerges as a viable treatment strategy for infections resistant to conventional antibiotics. A complex interplay of factors, including intracellular photosensitizer (PS) accumulation, photochemical reaction type, and oxygen levels, determines the efficacy of aPDT. Recent progress includes the development of modified PSs with enhanced lipophilicity and target-specific strategies to improve bacterial cell wall penetration and targeting.

Cloning of Three Aflatoxin B1 Oxidases of the Dipeptidyl Peptidase III Family and Evaluation of Their Potential for Practical Applications as Decontamination Enzymes.

Aflatoxin B1 (AFB1) produced by some species belongs to the most dangerous contaminants of animal feeds. Development of safe and cost efficient decontamination methods saving feed quality and nutritional value are of paramount importance. The use of recombinant AFB1-detoxifying microbial enzymes represents a promising biotechnological approach meeting the aforementioned requirements.

Metabolite concentrations and the expression profiles of the corresponding metabolic pathway genes in eggplant (Solanum melongena L.) fruits of contrasting colors.

Eggplant (Solanum melongena L.) ranks fifth in importance among vegetable crops of the Solanaceae family, in part due to the high antioxidant properties and polyphenol content of the fruit. Along with the popular purple-fruited varieties of S.

N-linked glycosylation affects catalytic parameters and fluctuation of the active center of Aspergillus awamori exo-inulinase.

Heterogeneous expression of enzymes allows large-scale production with reduced costs. Changes in glycosylation often occur due to changes in the expression host. In the study, the catalytic and biochemical properties of Aspergillus awamori exo-inulinase 1 are compared for A.

Dynamic features of virus protein 1 and substitutions in the 3-phenyl ring determine the potency and broad-spectrum activity of capsid-binding pyrazolo[3,4-d]pyrimidines against rhinoviruses.

Pyrazolo[3,4-d]pyrimidines represent one potent class of well tolerated and highly active rhinovirus (RV) inhibitors that act as capsid binders. The lead compound OBR-5-340 inhibits a broad-spectrum of RVs. Aiming to improve lead activity, we evaluated the impact of structural modifications in the 3-phenyl ring of OBR-5-340 on its potency and spectrum of anti-RV activity vitro.

Molecular mechanism of thiocyanate dehydrogenase at atomic resolution.

Some sulfur-oxidizing bacteria playing an important role in global geochemical cycles utilize thiocyanate as the sole source of energy and nitrogen. In these bacteria the process of thiocyanate into cyanate conversion is mediated by thiocyanate dehydrogenases - a recently discovered family of copper-containing enzymes with the three‑copper active site unique among the other copper proteins. To get a deeper insight into the structure and molecular mechanism of action of thiocyanate dehydrogenases we isolated, purified, and comprehensively characterized an enzyme from the bacterium Pelomicrobium methylotrophicum.

Photoinactivation of and by Near-Infrared Radiation Using a Trehalose-Conjugated Heptamethine Cyanine.

The spread of multidrug-resistant mycobacterium strains requires the development of new approaches to combat diseases caused by these pathogens. For that, photodynamic inactivation (PDI) is a promising approach. In this study, a tricarbocyanine (TCC) is used for the first time as a near-infrared (740 nm) activatable PDI photosensitizer to kill mycobacteria with deep light penetration.

The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division.

Aims: The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. Mycobacterium abscessus is associated with chronic lung deterioration in these populations. The intrinsic resistance of M.

Saturation Mutagenesis and Molecular Modeling: The Impact of Methionine 182 Substitutions on the Stability of β-Lactamase TEM-1.

Serine β-lactamase TEM-1 is the first β-lactamase discovered and is still common in Gram-negative pathogens resistant to β-lactam antibiotics. It hydrolyzes penicillins and cephalosporins of early generations. Some of the emerging TEM-1 variants with one or several amino acid substitutions have even broader substrate specificity and resistance to known covalent inhibitors.

Polyamines putrescine and spermidine as modulators of protein aggregation rate: The effect on DTT-induced aggregation of α-lactalbumin.

Protein aggregation is undesirable for cells due to its possible toxicity, and is also undesirable in biotechnology and pharmaceuticals. Polyamines are known to be capable of both suppressing and stimulating protein aggregation. In the present work polyamines (spermidine, putrescine) have been shown to alter the pathway of α-lactalbumin aggregation induced by dithiothreitol, leading to the formation of larger protein particles during the initial stages of aggregation and promoting the later stage of sticking of aggregates.

Single-point substitution F97M leads to in cellulo crystallization of the biphotochromic protein moxSAASoti.

To enhance the photoconversion performance of biphotochromic moxSAASoti protein, a substitution F97 M was introduced. In addition to enhancing the target properties, this substitution also resulted in the crystallization of the recombinant protein within living HeLa cells (also referred to as in cellulo crystallization). The phenomenon of protein crystallization in living cells is not unique, yet the mechanisms and application of in cellulo crystallization remain significant for further research.

A highly specific aptamer for the SARS-CoV-2 spike protein from the authentic strain.

DNA aptamers are oligonucleotides that specifically bind to target molecules, similar to how antibodies bind to antigens. We identified an aptamer named MEZ that is highly specific to the receptor-binding domain, RBD, of the SARS-CoV-2 spike protein from the Wuhan-Hu-1 strain. The SELEX procedure was utilized to enrich the initial 31-mer oligonucleotide library with the target aptamer.

Metagenomic evidence of a novel anammox community in a cold aquifer with high nitrogen pollution.

The process of anaerobic ammonium oxidation by nitrite (anammox) is a globally essential part of N cycle. To date, 8 Candidatus genera and more than 22 species of anammox bacteria have been discovered in various anthropogenic and natural habitats, including nitrogen-polluted aquifers. In this work, anammox bacteria were detected for the first time in the groundwater ecosystem with high anthropogenic nitrogen pollution (up to 1760 mg NO-N/L and 280 mg NH-N/L) and low year-round temperature (7-8 °C) in the zone of a uranium sludge repository.

Enhanced thermophilic high-solids anaerobic digestion of organic fraction of municipal solid waste with spatial separation from conductive materials in a single reactor volume.

Despite benefits such as lower water and working volume requirements, thermophilic high solids anaerobic digestion (THSAD) often fails due to the rapid build-up of volatile fatty acids (VFAs) and the associated drop in pH. Use of conductive materials (CM) can promote THSAD through stimulation of direct interspecies electron transfer (DIET), while the need for their constant dosing due to poor separation from effluent impairs economic feasibility. This study used an approach of spatially separating magnetite and granular activated carbon (GAC) from the organic fraction of municipal solid waste (OFMSW) in a single reactor for THSAD.

Efficacy of macozinone in mice with genetically diverse susceptibility to Mycobacterium tuberculosis infection.

Host heterogeneity in pulmonary tuberculosis leads to varied responses to infection and drug treatment. The present portfolio of anti-TB drugs needs to be boosted with new drugs and drug regimens. Macozinone, a clinical-stage molecule targeting the essential enzyme, DprE1, represents an attractive option.

Modulating mycobacterial envelope integrity for antibiotic synergy with benzothiazoles.

Developing effective tuberculosis drugs is hindered by mycobacteria's intrinsic antibiotic resistance because of their impermeable cell envelope. Using benzothiazole compounds, we aimed to increase mycobacterial cell envelope permeability and weaken the defenses of , serving as a model for Initial hit, BT-08, significantly boosted ethidium bromide uptake, indicating enhanced membrane permeability. It also demonstrated efficacy in the -zebrafish embryo infection model and -infected macrophages.

Nanobubble technology to enhance energy recovery from anaerobic digestion of organic solid wastes: Potential mechanisms and recent advancements.

Nanobubble (NB) technology has gained popularity in the environmental field owing to its distinctive characteristics and ecological safety. More recently, the application of NB technology in anaerobic digestion (AD) systems has been proven to promote substrate degradation and boost the production of biogas (H and/or CH). This review presents the recent advancements in the application of NB technology in AD systems.

The role of the correlated motion(s) of the chromophore in photoswitching of green and red forms of the photoconvertible fluorescent protein mSAASoti.

Wild-type SAASoti and its monomeric variant mSAASoti can undergo phototransformations, including reversible photoswitching of the green form to a nonfluorescent state and irreversible green-to-red photoconversion. In this study, we extend the photochemistry of mSAASoti variants to enable reversible photoswitching of the red form. This result is achieved by rational and site-saturated mutagenesis of the M163 and F177 residues.