Current Protein and Peptide Science - Volume 23, Issue 9, 2022

The major drawbacks of biofuel production at the commercial level are its low yield, nonavailability of feedstock, feedback inhibition, presence of inhibitory pathways in various organisms, and biofuel intolerance of organisms. The present review focuses on the implications of the CRISPRCas9 mediated gene editing tool to alter the genome of bacteria, algae, fungi, and higher plants for efficient biofuel production. Gene knockout and gene cassette insertions employing CRISPR-Cas9 in Saccharomyces cerevisiae and Kluyveromyces marxianus have resulted in enhanced production of bioethanol and 2-Phenyl ethanol in these organisms, respectively. Genomes of several bacterial strains were also modified to enhance ethanol and butanol production in them. CRISPR-Cas9 modification of microalgae has demonstrated improved total lipid content, a prerequisite for biofuel production. All over, CRISPR-Cas9 has emerged as a tool of choice for engineering the genome and metabolic pathways of organisms for producing industrial biofuel. In plant-based biofuel production, the biosynthetic pathways of lignin interfere with the satisfactory release of fermentable sugars thus hampering efficient biofuel production. CRISPR-Cas9 has shown a promising role in reducing lignin content in various plants including barley, switchgrass, and rice straw.

Cellular metabolic reprogramming driven by oncogenic mutations is considered as a hallmark in the development of malignant cells, and has been a focus over the past decade. A common theme emerging from these metabolic alterations is that tumor cells can acquire necessary nutrients from a nutrient-limited microenvironment and utilize them to sustain growth and unrestrained cellular division. However, this significant metabolic flexibility and the hostile microenvironment caused by the insufficient vascular exchange, depletion of nutrients, hypoxia, and accumulation of waste products, can inhibit the metabolism and immune activity of tumor-infiltrating lymphocytes and impose barriers to effective antitumor immunotherapies. In this perspective, we review the classical alterations in tumorigenesis- associated metabolic reprogramming and examine the functional contribution of these aberrant metabolisms to the establishment and maintenance of an immunosuppressive microenvironment. Furthermore, we explore the possible approaches to targeting on these metabolic pathways to achieve antitumor immunotherapy, as well as some hypothetical or ongoing combination therapeutic strategies that could, to a certain extent, biologically rationalize and broaden the utility of immune checkpoint inhibitors. Ultimately, we elucidate some dietary modifications that can limit tumor-specific nutritional requirements and maximize the cytotoxicity of other antineoplastic drugs.

Impairment in the function of insulin-producing pancreatic β-cells is a hallmark of both type 1 and 2 diabetes (T1D/T2D). Despite over a century of effort, there is still no precise treatment regimen available for acute diabetes. Enhancing the endogenous β-cells either by protecting them from apoptosis or dedifferentiation is a classic alternative to retaining the β-cell pool. Recent reports have acknowledged the protein homeostasis mediated by the ubiquitin-proteasome system as one of the essential components in maintaining the β-cell pool. Degradation of the targeted substrate by the proteasome is majorly regulated by the ubiquitination status of the targeted protein dictated by E3 ligases and deubiquitinase enzymes. Imbalance in the function of these enzymes results in the malfunction of β-cells and, subsequently, hyperglycemia. Ubiquitination involves the covalent attachment of one or more ubiquitin moieties to the target protein by E3 ubiquitin ligases and deubiquitinases (DUBs) are the enzymes that antagonize the action of E3 ligases. Knowing different E3 ligases and deubiquitinases in the process of differentiation and dedifferentiation of β-cells probably paves the way for designing novel modulators that enhance either the differentiation or abate the dedifferentiation process. In this review, we will discuss the importance of the balanced ubiquitination process, an understanding of which would facilitate the restraining of β-cells from exhaustion.

Peptide therapeutics represents one of the fastest-growing sectors in the pharmaceutical drugs pipeline, with an increasing number of regulatory approvals every year. Their pharmacological diversity, biocompatibility, high degree of potency and selectivity make them an attractive choice in several therapeutic areas, such as diabetes, cancer, immune, metabolic, cardiovascular and infectious diseases. However, the development of peptides as drugs presents its own set of challenges, necessitating extensive property optimization aimed at improving their drug-like properties and stability in biological environments. The discovery and development of innovative peptide therapeutic platforms entail the employment of several biophysical techniques, which monitor the structural as well as the functional integrity of peptides. Small structural changes of the bioactive peptides in response to the presence of various excipients can have a major impact on their pharmaceutical prowess, necessitating the use of analytical techniques for efficient quality control during development. Here we present some widely used methods, such as circular dichroism, fluorescence spectroscopy and multi-dimensional homo and heteronuclear nuclear magnetic resonance spectroscopy that form an integral part of therapeutic peptides development. The application of combination biophysical platforms ensures the maintenance of the appropriate folded structure, which is a prerequisite for the safety and efficacy of peptide pharmaceuticals.