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The fungal P450s catalyze vital monooxygenation reactions in primary and secondary metabolism, which may lead to the production of diverse secondary metabolites. Many of these, such as from the family of trichothecenes, involve in biocontrol activities. The diversified nature of fungal P450 monooxygenases makes their host organisms adoptable to various ecological niches. The available genome data analysis provided an insight into the activity and mechanisms of the fungal P450s. However, still more structural and functional studies are needed to elucidate the details of its catalytic mechanism, and the advance studies are also required to decipher further about their dynamic role in various aspects of trichothecene oxygenations. This mini review will provide updated information on different fungal P450 monooxygenases, their genetic diversity, and their role in catalyzing various biochemical reactions leading to the production of plant growth promoting secondary metabolites.

Next-generation sequencing has allowed us to explore new methods, where comparative and population genomics can be used simultaneously. Keeping this in mind, we surveyed and analyzed the frequency and distribution of microsatellites in the Indian gharial (Gavialis gangeticus) and compared it with American alligator (Alligator mississippiensis) and saltwater crocodile (Crocodylus porosus) to enrich them with genomic resources. The Indian gharial has a low frequency, relative abundance (RA), and relative density (RD) of microsatellites as compared to other crocodilians. RA and RD were positively correlated with the GC content of genomic and transcriptomic sequences. The genomic sequences were dominated by dinucleotide repeats, whereas the transcriptomic sequences had an excess of trinucleotide repeats. Motif conservation studies among the three crocodilians revealed conservation of 69.2% of motifs. Species-specific unique motifs identified in this study could be used as molecular probes for species identification. A total of 67,311 primers were designed in all three species to enrich the crocodilians with genomic resources. The genomic resources developed in this study could accelerate diversity analysis within its individuals to design a proper mating plan to reduce inbreeding stress and further improve the species.

Nisin inhibits bacterial growth by generating pores in cell membrane and interrupting cell-wall biosynthesis through specific lipid II interaction. However, the role of the hinge region and C-terminus residues of the peptide in antibacterial action of nisin is largely unknown. Here, using molecular dynamics simulations and experimental approach, we report that at high concentration regimes of nisin, interaction with phospholipids may equally deform the bacterial cell membranes even under significantly varying amounts of lipid-II. Membrane thinning, destabilization and decrease in lipid density depend on the degree of oligomerization of nisin. Growth kinetics of Bacillus subtilis and Escherichia coli interestingly show recovery by extended lag phase under low concentrations of nisin treatment while high concentrations of nisin caused decrease in cell viability as recorded by striking reduction in membrane potential and surface area. The significant changes in the dipole potential and fluorescence anisotropy were observed in negatively charged membranes in the absence of lipid-II with increasing concentration of nisin. The identical correlation of cell viability, membrane potential dissipation and morphology with the concentration regime of nisin, in both Bacillus subtilis (lipid II rich) and Escherichia coli (lipid II impoverished), hints at a non-specific physical mechanism where degree of membrane deformation depends on degree of crowding and oligomerization of nisin.

Diabetic retinopathy (DR) is a vision-threatening, chronic, and challenging eye disease in the diabetic population. Despite recent advancements in the clinical management of diabetes, DR remains the major cause of blindness in working-age adults. A better understanding of the molecular and cellular basis of DR development will aid in identifying therapeutic targets. Emerging pieces of evidence from recent research in the field of ER stress have demonstrated a close association between unfolded protein response (UPR)-associated cellular activities and DR development. In this minireview article, we shall provide an emerging understating of how UPR influences DR pathogenesis at the cellular level.

Drug resistance is a major concern due to the evolution and emergence of pathogenic bacterial strains with novel strategies to resist the antibiotics in use. Mycobacterium tuberculosis (Mtb) is one of such pathogens with reported strains, which are not treatable with any of the available anti-TB drugs. This scenario has led to the need to look for some novel drug targets in Mtb, which may be exploited to design effective treatment strategies against the infection. The goal of this review is to discuss one such class of emerging drug targets in Mtb. MmpL (mycobacterial membrane protein large) proteins from Mtb are reported to be involved in multi-substrate transport including drug efflux and considered as one of the contributing factors for the emergence of multidrug-resistant strains. MmpL proteins belong to resistance nodulation division permeases superfamily of membrane transporters, which are viably and pathogenetically important and their inhibition could be lethal for the bacteria.

Here, we have analyzed the enzyme ornithine carbamoyltransferase (OCTase) in different classes of microorganisms belonging to psychrophiles, mesophiles and thermophiles. This OCTase catalyzes the formation of citrulline from carbamoyl phosphate (CP) and ornithine (ORN) in arginine biosynthesis pathway and has certain unique adaptations to regulate metabolic pathways in extreme conditions. The tertiary structure of OCTase showed two binding domains, the CP domain and ORN-binding domain at N and C terminals, respectively. We propose general acid–base catalysis in Pseudomonas gessardii between His259 and Asp220 in which later may act as a recipient of proton in the process. The comparative docking analysis showed that substrate-binding loops have been evolved to accommodate their lifestyles across the physiological temperature range where two substrates bind on two distinct loops in psychrophiles and mesophiles, whereas both the substrates bind on a single-substrate-binding loop in thermophiles and bring down the flexibility of the active site pocket to improve its evolutionary fitness.

Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions. However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order. When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans. We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures. When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures. N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions. Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.

Fungi present in rhizosphere produce trichothecene metabolites which are small in size and amphipathic in nature and some of them may cross cell membranes passively. Hypocreaceae family of rhizosphere fungi produce trichothecene molecules, however it is not a mandatory characteristic of all genera. Some of these molecules are also reported as growth adjuvant, while others are reported as deleterious for the plant growth. In this review, we are exploring the roles of these compounds during plant-microbe interactions. The three-way interaction among the plants, symbiotic microbial agents (fungi and bacteria), and the pathogenic microbes (bacteria, fungi) or multicellular pathogens like nematodes involving these compounds may only help us to understand better the complex processes happening in the microcosm of rhizosphere. These metabolites may further modulate the activity of different proteins involved in the cell signalling events of defence-related response in plants. That may induce the defence system against pathogens and growth promoting gene expression in plants, while in animal cells, these molecules have reported biochemical and pharmacological effects such as inducing oxidative stress, cell-cycle arrest and apoptosis, and may be involved in maintenance of membrane integrity. The biochemistry, chemical structures and specific functional group-mediated activity of these compounds have not been studied in details yet. Few of these molecules are also recently reported as novel anti-cancer agent against human chondrosarcoma cells.

Microbial biofilm indicates a cluster of microorganisms having the capability to display drug resistance property, thereby increasing its proficiency in spreading diseases. In the present study, the antibiofilm potential of thymoquinone, a black seed–producing natural molecule, was contemplated against the biofilm formation by Pseudomonas aeruginosa. Substantial antimicrobial activity was exhibited by thymoquinone against the test organism wherein the minimum inhibitory concentration of the compound was found to be 20 μg/mL. Thereafter, an array of experiments (crystal violet staining, protein count, and microscopic observation, etc.) were carried out by considering the sub-MIC doses of thymoquinone (5 and 10 μg/mL), each of which confirmed the biofilm attenuating capacity of thymoquinone. However, these concentrations did not show any antimicrobial activity. Further explorations on understanding the underlying mechanism of the same revealed that thymoquinone accumulated reactive oxygen species (ROS) and also inhibited the expression of the quorum sensing gene (lasI) in Pseudomonas aeruginosa. Furthermore, by taking up a combinatorial approach with two other reported antibiofilm agents (tetrazine-capped silver nanoparticles and tryptophan), the antibiofilm efficiency of thymoquinone was expanded. In this regard, the highest antibiofilm activity was observed when thymoquinone, tryptophan, and tetrazine-capped silver nanoparticles were applied together against Pseudomonas aeruginosa. These combinatorial applications of antibiofilm molecules were found to accumulate ROS in cells that resulted in the inhibition of biofilm formation. Thus, the combinatorial study of these antibiofilm molecules could be applied to control biofilm threats as the tested antibiofilm molecules alone or in combinations showed negligible or very little cytotoxicity.

Multidrug resistance mechanism of microorganisms towards conventional antimicrobials nowadays faces a common health problem. So, searching and development of new antibacterials are in the frontier areas of biochemistry. Functionalizations of various natural products or synthesis of compounds through molecular modeling followed by virtual screening are the ways to obtain potential leads. Chrysin is one of the plant secondary metabolites and is ubiquitously present in majority of plants. It has multi-dimensional potentiality however, with a very low bioavailability causing a very low efficacy. Very few chrysin derivatives possessing antimicrobial activity with a low anti-biofilm efficacy have been found in the literature. Thus, it has been attempted to synthesize a series of new chrysin derivatives (CDs). In this study, twenty-two new derivatives have been synthesized via its 7-OH modulation and antibiofilm activity was evaluated against a model bacterium viz. Escherichia coli MTCC 40 (Gram negative). Eleven CDs coded as 2a, 2b, 2c, 2e, 2f, 2g, 2h, 2i, 3j, 3k and 3l have been found more potent compared to chrysin (precursor of CDs) against planktonic form of E. coli. Biofilm inhibition studies indicated a noteworthy results for 2a (93.57%), 2b (92.14%), 2f (92.14%) and 3l (93.57%) compared to chrysin (33.57%). E. coli motility was also highly restricted by 2a, 2b, 2f and 3l than chrysin at their sub-inhibitory concentrations. Solubility studies indicated an extended-release of 2a, 2b, 2f and 3l in physiological systems. Relatively higher bioavailability of 2a, 2b, 2f and 3l than chrysin was revealed from the dissolution experiments and was further validated through in silico ADME-based SAR analysis. Hence, this study is more interesting in regard to antibacterial potentiality of chrysin derivatives against Escherichia coli MTCC 40 (Gram negative). Thus, this article might be useful for further design and development of new leads in the context of biofilm-associated bacterial infections.Graphic abstract