Current Biotechnology - Volume 12, Issue 2, 2023

Ribonucleic acid (RNA) and its types have emerged as master regulators of biological processes and expanded knowledge regarding the role of RNA in the gene expression inside the cell have dramatically changed the therapeutic strategies in the past few years. RNA has become a focus for developing novel therapeutic schemes and hence RNA-based therapies, particularly in viral diseases have become more enthralling and promising. It is due to the fact that RNA offers various advantages in disease management as it can be edited and customized in its various forms such as secondary and tertiary structures. Principles and mechanisms regarding RNA therapeutics are well described in volumes, however, the information regarding long-awaited RNA-based drug development and potential hurdles as well as barriers in the way is still scattered. In this regard, these agents are required to overcome a plethora of barriers such as stability of drug targets, immunogenicity, adequate binding, targeted delivery, etc. to become effective drugs. Most of the trials are changing their way from in-vitro to in-vivo studies and it is not far away when RNA-based therapeutics will find their way from bench to bedside. In this communication, the authors give a brief review of important recent advances in above said domains of miRNA therapeutics.

Regular blood cholesterol control is an integral part of healthcare for detecting cardiovascular issues immediately. Existing procedures are mostly intrusive and necessitate the collection of blood samples. Furthermore, because of the danger of infection, bruising, and/or haematoma, this measurement method may not be appropriate for continuous or regular examinations. As a result, an alternate option is required, which is known as the noninvasive (NI) approach that does not necessitate the collection of blood samples. Because NI approaches give painless and precise answers, they can be used in place of intrusive procedures. This review article includes a comprehensive investigation on NI methodologies and various NI approaches for detecting cholesterol in the bloodstream. It is important to note that medical system possibilities are changing due to the algorithms for NI techniques, which ultimately project the need for patient monitoring via the internet of medical things (IoMT) and artificial intelligence (AI).

Species within the actinobacterial genus Streptomyces represent one of the most gifted natural chemists in the microbial world. Their specialized metabolites attract the interest of the pharmaceutical industry as a source of novel drugs. A majority of these molecules pose an insurmountable challenge for economically justified production via chemical synthesis. Therefore, submerged fermentation-based isolation of such molecules often remains the only viable way to obtain them. This in turn fuels interest in process development programs aiming to maximize the yield of specialized metabolite per volume unit of fermentation medium. Along with the optimization of the medium and the fermentation mode itself, strain improvement remains an important part of an overall process development endeavor. An improved strain can be generated via application of traditional approaches of selection for random or induced mutants and genomics-enabled genetic engineering methods. Here I focus on a specific class of mutations with the gene rpsL for ribosomal protein S12, which often confer resistance to streptomycin in bacteria and upregulate specialized metabolism in Streptomyces. The review will portray the evolution of our understanding of the mechanisms behind rpsL mutations, as well as how technological advances change the way these mutations are introduced into the genomes of interest.

Background: α-Synuclein has become the main therapeutic target in Parkinson's disease and related Synucleinopathies since the discovery of genetic associations between α-Synuclein and Parkinson's disease risk and the identification of aggregated α-Synuclein as the primary protein constituent of Lewy pathology two decades ago. The two new peptides K84s (FLVWGCLRGSAIGECVVHGGPPSRH) and K102s (FLKRWARSTRWGTASCGGS) have recently been found to significantly reduce the oligomerization and aggregation of α-Synuclein. However, it is still unclear where these peptides interact with α-Synuclein at the moment. Objective: To examine the locations where K84s and K102s interact with α-Synuclein. Methods: In this investigation, the PEPFOLD3 server was used to generate the 3-D structures of the K84s and K102s peptides. Using the PatchDock web server, the two peptides were docked to the α- Synuclein molecule. After that, 50 ns of Molecular Dynamics (MD) simulations using the Amberff99SBildn force field were performed on the two resulting docked complexes. The two complexes' structure, dynamics, energy profiles, and binding modes were identified through analysis of the respective MD simulation trajectories. By submitting the two complexes' lowest energy structure to the PDBsum website, the interface residues in the two complexes were identified. The per residue energy decomposition (PRED) analysis using the MM-GBSA technique was used to calculate the contributions of each residue in the α-Synuclein of (α-Synuclein-K84s/K102s) complexes to the total binding free energy. Results: The binding of the two peptides with the α-Synuclein was demonstrated to have high binding free energy. The binding free energies of the (α-Synuclein-K84s) and (α-Synuclein-K102s) complexes are -33.61 kcal/mol and -40.88 kcal/mol respectively. Using PDBsum server analysis, it was determined that in the (α-Synuclein-K84s) complex, the residues GLY 25, ALA 29, VAL 49, LEU 38, VAL 40, GLU 28, GLY 47, LYS 32, GLU 35, GLY 36, TYR 39, VAL 48 and VAL 26 (from α-Synuclein) and SER 23, LEU 7, ILE 12, HIS 25, PHE 1, HIS 18, CYS 6, ARG 24, PRO 21 and ARG 8 (from K84s peptide) were identified to be present at the interface. In the (α-Synuclein- K102s) complex, the residues VAL 40, GLY 36, GLU 35, TYR 39, LYS 45, LEU 38, LYS 43, VAL 37, THR 44, VAL 49, VAL 48, and GLU 46 (from α-Synuclein) and ARG 10, GLY 12, GLY 18, SER 15, THR 13, SER 19, TRP 11, ALA 14, CYS 16, ARG 7, ARG 4 and GLY 17 (from K102s peptide) were identified to be present at the interface. The PRED analysis revealed that the residues PHE 1, LEU 7, ILE 12, LEU 2, VAL 3, GLY 5, and PRO 21 of the K84s peptide and residues VAL 48, ALA 29, VAL 40, TYR 39, VAL 49, VAL 26 and GLY 36 of α-Synuclein in the (α- Synuclein-K84s) complex are responsible for the intermolecular interaction. The residues ARG 4, ARG 10, TRP 11, ALA 14, SER 15, CYS 16 and SER 19 of the K102s peptide and residues GLU 46, LYS 45, VAL 49, GLU 35, VAL 48, TYR 39, and VAL 40 of α-Synuclein are responsible for the intermolecular interaction in the instance of the (α-Synuclein-K102s) complex. Additionally, it has been found that a sizable portion of the helical structure is preserved when α-Synuclein is in a complex form with the K84s and K102s peptides. Conclusion: Taken together the data implies that the two new peptides investigated here could be suitable candidates for future therapeutic development against α-Synuclein aggregation.

Background: Lipase is one of the most well-known and essential biocatalysts in the detergent, food, and pharmaceutical industries. Microbial lipase sources such as yeasts are applicable due to their stability in harsh conditions. Objective: In this study, the effect of temperature, initial pH, and incubation time were investigated to improve the extracellular lipase production by yeast, named Zygoascus hellenicus strain MZ_574439 ^T. Methods: Strain MZ_574439 ^T has already been isolated and registered from Iran. In the current project, strain MZ_574439 ^T with 99% similarity to gt;Z. hellenicus was isolated from water samples. Results: Our findings showed that the isolated strain has a remarkable difference from its close phylogenetic species in the production of lipase and can produce extracellular lipase up to 7.2 U/ml while the Z. hellenicus has no ability of lipase production. The isolated strain was not able to produce other hydrolytic enzymes. The enzyme activity results showed that the best activity for the isolated lipase is pH= 7 and 37°C. The best stability condition for the enzyme occurs at 50°C and pH =7. Conclusion: From the current study, it can be concluded that Z. hellenicus produces lipase. The lipase enzyme production was optimized with different physiological conditions. Yeast extract could be a better source for maximum lipase production.

Introduction: Intrinsically Disordered Proteins (IDPs) are natively unstructured proteins. Interestingly, IDPs are ubiquitous and play key roles in cellular and proteins functions. While IDPs are studied in some proteomes, many remain to be uncovered. Methods: The data were retrieved from MobiDB database version 4. Intrinsic disorder predictions are made with various prediction tools. We focus on IUpred-L predictions. Results: Here, we have explored the first large-scale study of IDPs in T. turgidum. Additionally, a comparative analysis of T. turgidum and T. aestivum IDPs was performed for highlighting the disorder use in each species. The data indicated that the T.turgidum proteome is significantly more disordered than the T. aestivum proteome. Gene ontology analysis revealed that IDPs in T. turgidum are mainly catalytic and binding proteins involved in regulation of cellular and metabolic processes. Conclusion: These findings may constitute a starting point for deeper understanding of IDP roles in stress tolerance and the mechanisms underlying the adaptation capacities differences between T. turgidium and related species.