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An Overview of Protease Inhibitors
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Veena Sreedharan, K.V. Bhaskara Rao
Actinomycetes are bacteria that are nonmotile, aerobic, and gram-positive G+C (70 to 80%) and that have a relationship with bacteria based on 16s ribosomal arrangement studies. They are members of the Actinomycetales order, which produces substrate mycelium as well as aerial mycelia and spores. Aerial mycelium spore-bearing hyphae are slightly larger than substrate mycelium hyphae. Actinobacteria’s aerial mycelium produces sporophores with a variety of structures. The spores are unaffected by drying and can live in soil for lengthy periods. This phase of the life cycle confers resilience to the soil’s harsh environmental conditions, such as nutrient deficiency and water scarcity. Actinobacteria have a wide range of phenotypes and can be found in a variety of natural settings (Williams et al., 1983). They show a crucial part in the production of a wide range of medications that are vital for our nutrition and health. Actinobacteria, primarily the species Streptomyces and Micromonospora, are known to be the source of about 60–70% of the antibiotics available in the world (Jensen et al., 1991). The list of antibiotics produced by several Actinobacteria with excellent antibacterial activity is shown in Table 19.3.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Dynemicin A (Figure 5.57) was first isolated in the mid-1980s from the bacterium Micromonospora chernisa found growing in a soil sample from the state of Gujarat, India. Although it was initially isolated as a potential dye due to its bright color, its cytotoxic properties were discovered later. The Bristol-Myers Pharmaceutical Company in Japan elucidated its structure in the late 1980s based on X-ray diffraction studies of the closely related derivative triacetyl-dynemicin A. The distinctive bright purple color of the molecule is due to the anthraquinone chromophore within its structure.
Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Gentamicin is a broad-spectrum aminoglycoside antibiotic produced by fermentation of Micromonospora purpurea or M. echinospora. It is an antibiotic complex consisting of four major (C1, C1a, C2, and C2a) and several minor components. Gentamicin is indicated for treatment of serious infections caused by susceptible strains of Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), E. coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative). This antibiotic is also used in topical pharmaceuticals for the treatment of superficial skin and eye infections. In pharmaceutical products, gentamicin is employed as gentamicin sulfate (CAS number 1405-41-0, EC number 215-778-9, molecular formula C19H40N4O10S) (1).
A glyco-engineering approach for site-specific conjugation to Fab glycans
Published in mAbs, 2023
Maria L. Jaramillo, Traian Sulea, Yves Durocher, Mauro Acchione, Melissa J. Schur, Anna Robotham, John F. Kelly, Marie-France Goneau, Alma Robert, Yuneivy Cepero-Donates, Michel Gilbert
Sialic acid was removed by treating 9.6 mg of cetuximab with 0.96 unit of a recombinant sialidase from Micromonospora viridifaciens (construct MNV-02) for 2 h at 37°C in 50 mM Hepes pH 6.5. Removal of the sialic acid was confirmed by isoelectrofocusing using a PhastSystem (GE Healthcare Life Sciences), PhastGel IEF 3–9 and staining with Coomassie blue. The MNV-02 sialidase includes a 6-His tag and was removed by binding to 0.6 mL of Nickel Sepharose excel resin (GE Healthcare Life Sciences) while cetuximab was recovered in the flowthrough. An assay for sialidase activity measured residual activity, which required removal by binding of the cetuximab to a HiTrap Protein A column (GE Healthcare Life Sciences) as described below. In order to enhance the level of galactosylation, galactose was added using a recombinant version of the human B4GalT1 expressed in E. coli. The reaction mix included approximately 9 mg of de-sialylated cetuximab, 500 mU of B4GalT1, 10 mM MnCl2, 10 mM UDP-Gal, 50 mM Hepes pH 6.5 and 100 mM NaCl. The reaction was performed at 37°C for 24 h. The cetuximab was purified by applying half of the reaction mix to a 1 mL Protein A column equilibrated with PBS buffer pH 7.5 (2 separate runs total were performed). The cetuximab was eluted with 100 mM citrate buffer pH 3 and the buffer was replaced with PBS pH 7.5 by desalting on a 5 mL HiTrap desalting column (GE Healthcare Life Sciences). The material was concentrated to 2.94 mg/mL (total of 7.64 mg recovered) using an Amicon Ultra-4 centrifugal filter unit with a 10,000 NMWL.
Recent advances and future perspectives in the pharmacological treatment of Candida auris infections
Published in Expert Review of Clinical Pharmacology, 2021
Daniele R. Giacobbe, Laura Magnasco, Chiara Sepulcri, Malgorzata Mikulska, Philipp Koehler, Oliver A. Cornely, Matteo Bassetti
Turbinmicin was discovered through the screening of 1482 actinobacteria from marine invertebrates and subsequent challenge in vitro for activity against C. albicans. Turbinmicin was isolated from a sea squirt microbiome constituent, Micromonospora spp., and belongs to highly oxidized type II polyketides [112]. Its antifungal activity was tested against 39 fungi, including one isolate of fluconazole-resistant and micafungin-resistant C. auris, showing a MIC of 0.25 mg/L [112]. Turbinmicin was also evaluated in a neutropenic murine model of C. auris bloodstream infection, showing a greater reduction in fungal load in comparison with micafungin. Sec14p, a transfer protein essential for cellular trafficking, was identified as the antifungal target of turbinmicin [112].
Potential of rare actinomycetes in the production of metabolites against multiple oxidant agents
Published in Pharmaceutical Biology, 2018
Fatemeh Mohammadipanah, Mana Momenilandi
Actinobacterial strains (52 strains) from 11 genera of Nonomuraea sp., Micromonospora sp., Saccarothrix sp., Nocardiopsis sp., Amycolatopsis sp., Kribbella sp., Nocardia sp., Actinophytocola sp., Streptosporangium sp., Promicromonospora sp. and Actinokineospora sp. were obtained from the University of Tehran Microorganisms Collection (UTMC). All of the strains were preserved in the vapor of liquid nitrogen and as glycerol suspensions (30% W/V) at −70 °C.