Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems.

Heterologous expression of L-asparaginase (L-ASNase) has become an important area of research due to its clinical and food industry applications. This review provides a comprehensive overview of the molecular and metabolic strategies that can be used to optimize the expression of L-ASNase in heterologous systems. This article describes various approaches that have been employed to increase enzyme production, including the use of molecular tools, strain engineering, and in silico optimization. The review article highlights the critical role that rational design plays in achieving successful heterologous expression and underscores the challenges of large-scale production of L-ASNase, such as inadequate protein folding and the metabolic burden on host cells. Improved gene expression is shown to be achievable through the optimization of codon usage, synthetic promoters, transcription and translation regulation, and host strain improvement, among others. Additionally, this review provides a deep understanding of the enzymatic properties of L-ASNase and how this knowledge has been employed to enhance its properties and production. Finally, future trends in L-ASNase production, including the integration of CRISPR and machine learning tools are discussed. This work serves as a valuable resource for researchers looking to design effective heterologous expression systems for L-ASNase production as well as for enzymes production in general.

Antibiotic resistance in agriculture: Perspectives on upcoming strategies to overcome upsurge in resistance.

Antibiotic resistance is a massive problem rising constantly and spreading rapidly since the past decade. The major underlying mechanism responsible for this problem is an overuse or severe misuse of antibiotics. Regardless of this emerging global threat, antibiotics are still being widely used, not only for treatment of human infections, but also to a great extent in agriculture, livestock and animal husbandry. If the current scenario persists, we might enter into a post-antibiotic era where drugs might not be able to treat even the simplest of infections. This review discusses the current status of antibiotic utilization and molecular basis of antibiotic resistance mechanisms acquired by bacteria, along with the modes of transmittance of the resultant resistant genes into human pathogens through their cycling among different ecosystems. The main focus of the article is to provide an insight into the different molecular and other strategies currently being studied worldwide for their use as an alternate to antibiotics with an overall aim to overcome or minimize the global problem of antibiotic resistance.

Influence of Silicon on Biocontrol Strategies to Manage Biotic Stress for Crop Protection, Performance, and Improvement.

Silicon (Si) has never been acknowledged as a vital nutrient though it confers a crucial role in a variety of plants. Si may usually be expressed more clearly in Si-accumulating plants subjected to biotic stress. It safeguards several plant species from disease. It is considered as a common element in the lithosphere of up to 30% of soils, with most minerals and rocks containing silicon, and is classified as a "significant non-essential" element for plants. Plant roots absorb Si, which is subsequently transferred to the aboveground parts through transpiration stream. The soluble Si in cytosol activates metabolic processes that create jasmonic acid and herbivore-induced organic compounds in plants to extend their defense against biotic stressors. The soluble Si in the plant tissues also attracts natural predators and parasitoids during pest infestation to boost biological control, and it acts as a natural insect repellent. However, so far scientists, policymakers, and farmers have paid little attention to its usage as a pesticide. The recent developments in the era of genomics and metabolomics have opened a new window of knowledge in designing molecular strategies integrated with the role of Si in stress mitigation in plants. Accordingly, the present review summarizes the current status of Si-mediated plant defense against insect, fungal, and bacterial attacks. It was noted that the Si-application quenches biotic stress on a long-term basis, which could be beneficial for ecologically integrated strategy instead of using pesticides in the near future for crop improvement and to enhance productivity.

Molecular strategies to increase keratinase production in heterologous expression systems for industrial applications.

Keratinase is an important enzyme that can degrade recalcitrant keratinous wastes to form beneficial recyclable keratin hydrolysates. Keratinase is not only important as an alternative to reduce environmental pollution caused by chemical treatments of keratinous wastes, but it also has industrial significance. Currently, the bioproduction of keratinase from native keratinolytic host is considered low, and this hampers large-scale usage of the enzyme. Straightforward approaches of cloning and expression of recombinant keratinases from native keratinolytic host are employed to elevate the amount of keratinase produced. However, this is still insufficient to compensate for the lack of its large-scale production to meet the industrial demands. Hence, this review aimed to highlight the various sources of keratinase and the strategies to increase its production in native keratinolytic hosts. Molecular strategies to increase the production of recombinant keratinase such as plasmid selection, promoter engineering, chromosomal integration, signal peptide and propeptide engineering, codon optimization, and glycoengineering were also described. These mentioned strategies have been utilized in heterologous expression hosts, namely, Escherichia coli, Bacillus sp., and Pichia pastoris, as they are most widely used for the heterologous propagations of keratinases to further intensify the production of recombinant keratinases adapted to better suit the large-scale demand for them. KEY POINTS: • Molecular strategies to enhance keratinase production in heterologous hosts. • Construction of a prominent keratinolytic host from a native strain. • Patent analysis of keratinase production shows rapid high interest in molecular field.

Review of STAT3 (Signal Transducers and Activators of Transcription) in head and neck cancer.

STATs can be activated independently of JAKs, most notably by c-Src kinases. In cancer cells, STAT3 and STAT5 activation leads to the increased expression of downstream target genes, leading to increased cell proliferation, cell survival, angiogenesis, and immune system evasion. STAT3 and STAT5 are expressed and activated in head and neck squamous cell carcinoma where they contribute to cell survival and proliferation. STATs can be activated by a number of signal transduction pathways, including the epidermal growth factor receptor (EGFR), nicotinic receptor, interleukin (IL) receptor, and erythropoietin receptor pathways. Identifying agents that inhibit STAT-3, a cytosolic transcription factor involved in the activation of various genes implicated in tumor progression is a promising strategy for cancer chemoprevention. Several approaches have been used to inhibit STAT3 in the hope of developing an antitumor agent. Although several STAT3-specific agents are promising, none are in clinical development, mostly because of drug delivery and stability issues.