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Industrial Applications of Bacterial Enzymes
Published in Pankaj Bhatt, Industrial Applications of Microbial Enzymes, 2023
Lipase obtained from genera including Pseudomonas, Bacillus, and Burkholderia is utilized in various processes, like dietary triglycerides, cell signaling, and inflammation [43, 44]. Enzymes for the production of 6-amino penicillanic acid antimicrobials by penicillin acylase are obtained from Bacillus megaterium, Alcaligenes, and E. coli [45, 46, 47, 48, 49, 50]. Adenosine deaminase (ADA) obtained from Bacillus sp. J-89 is an enzyme that helps in the metabolism of purine, making inosine and free ammonia by the hydrolytic breakdown of adenosine. ADA regulation is targeted as a probable therapeutic agent to treat various infections related to viruses and lymphoproliferative disorders [51]. Treatment of several diseases, like severe combined immunodeficiency disease (SCID), is reported by the help of Adenosine deaminase (ADA) enzyme [52]. This enzyme plays an important role in breakdown of excess adenosine present in the patients that leads to diminish their toxicity of the raised adenosine levels to the patient.
Genome Editing and Gene Therapies: Complex and Expensive Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Gaudelli et al. (2017) developed programmable base editing of A•T to G•C (adenosine base editor (ABE) with an efficiency of 50% and high product purity and indel rates of <0.1%. These results were obtained with an evolved (seven rounds) transfer RNA adenosine deaminase (from E. coli TadA; tRNA-specific adenosine deaminase) to act on genomic DNAs after fusion with a catalytically inactive CRISPR/dCas9 mutant. Base editing results could be improved by introducing mutations (TadA: A106V and D108N) and by TadA dimerization. TadA catalyzes the deamination of adenosine to inosine (see the scheme on the previous page; adenosine and inosine are given as monophosphate residues). Inosine preferentially base pairs with cytosine and is consequently read or replicated as G.
Medium Design for Cell Culture Processing
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
Thymidine and hypoxanthine are commonly used as pyrimidine and purine sources in contemporary media. They are readily linked to a ribose 5-phosphate in the cell to become inosine monophosphate (IMP) and TMP. IMP enters the synthetic pathway to make AMP and GMP, which are further phosphorylated into ATP and GTP. TMP is converted to UMP and CMP. If hypoxanthine is not available in the medium, de novo synthesis is the primary source and must be sufficiently active to sustain cell growth since the salvage pathway only recycles the base “salvaged” from nucleic acid degradation, but does not generate the nucleosides needed for proliferation. In de novo synthesis, the four nitrogen atoms in each purine ring are derived from glutamine, aspartate, and glycine, while obtaining carbons requires CO2, formate, glycine, and folic acid. The de novo synthesis of pyrimidine similarly requires glutamine, aspartic acid, and CO2. One can see that without a sufficient supply of hypoxanthine, many precursors will be needed for nucleoside biosynthesis.
Investigation of the embryo-toxicity of the antiviral drug “Ribavirin” in Wistar rats during different gestation periods
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Mohamed Magdy, Abd El Wahab El Ghareeb, Taha M. A. Eldebss, Heba Ali Abd El Rahman
Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a water-soluble, guanosine nucleoside analog that mimics other purines, including inosine and adenosine [1]. It is a broad-spectrum direct antiviral agent (DAA) authorized in 1986 [2]. Ribavirin demonstrated antiviral efficacy against DNA and RNA viruses in numerous animal infection models [1]. In addition, ribavirin has been utilized to treat Lassa fever virus infection and other viruses [3]. However, ribavirin given to adult female rats resulted in severe ovary damage. These genotoxic effects of ribavirin may induce infertility in pregnant rats throughout the reproductive phases [4], and ribavirin at doses of 60 and 90 mg/kg/day resulted in statistically significant and/or dose-related increases in fetal resorptions, malformations, and decreased postnatal survival [5].
Comparative proteomic analysis revealed the metabolic mechanism of excessive exopolysaccharide synthesis by Bacillus mucilaginosus under CaCO3 addition
Published in Preparative Biochemistry & Biotechnology, 2019
Hongyu Xu, Zhiwen Zhang, Hui Li, Yujie Yan, Jinsong Shi, Zhenghong Xu
Nucleotides are involved in almost all biochemical processes of the cells; these molecules are precursors of nucleic acid biosynthesis and intermediates of many biosynthesis processes.[34] The three enzymes (polyribonucleotide nucleotidyltransferase, dihydropyrimidinase, and inosine 5′-monophosphate dehydrogenase) were all down-regulated with CaCO3 addition. In the control group, the expression of nucleotide metabolism-related proteins was relatively enhanced and indicates that the substrate used at this time was mainly adopted to maintain the growth of cells themselves. Nucleotide metabolism was inhibited under CaCO3 addition. The utilization of the substrate was high, and additional carbon flux flowed to the direction of polysaccharide synthesis with the growth and reproduction of the substrate.
Recombinogenic, genotoxic, and cytotoxic effects of azathioprine using in vivo assays
Published in Journal of Toxicology and Environmental Health, Part A, 2021
A. V. D. Melo Bisneto, L. C. D. Oliveira, A. Silva Fernandes, L. S. Silva, J. H. Véras, C. G. Cardoso, Carolina R. E Silva, A. V. de Moraes Filho, C. C. Carneiro, L. Chen-Chen
To promote pharmacological effects, following oral administration, the Aza molecule is cleaved by enzymatic actions of glutathione transferases, giving rise to the nitroimidazole group and 6-mercaptopurine (6-MP). Subsequently, 6-MP is transformed by hypoxanthine-phosphoribosyl transferase into 6-thioinosine monophosphate, which is converted to 6-thioxanthine monophosphate (6-TXPM) by inosine-5-monophosphate dehydrogenase. Finally, through the action of the enzyme 5-monophosphate synthase, 6-TXPM generated 6-thioguanine (6-TG) which is incorporated into DNA as a false metabolite, blocking the synthesis of lymphocytes (FDA 2011).