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Industrial biotechnology
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2018
Streptomycin and other antibiotics are produced using strains of Streptomyces griseus. Spores of this actinomycete are inoculated into a medium to establish a culture with a high mycelial biomass for introduction into an inoculum tank, with subsequent use of the mycelial inoculum to initiate the fermentation process in the production tank. The medium contains soybean meal (N-source), glucose (C-source), and NaCl. The process is carried out at 28°C, and the maximum production is achieved at pH range of 7.6–8.0. High agitation and aeration are needed. The process lasts for about 10 days. The classic fermentation process involves three phases. During the first phase, there is a rapid growth of the microbe with the production of mycelial biomass. Proteolytic activity of the microbe releases ammonia (NH3) to the medium from the soybean meal, causing a rise in pH. During this initial fermentation phase, there is little production of streptomycin. During the second phase, there is little additional production of mycelium, but the secondary metabolite, streptomycin, accumulates in the medium. The glucose and NH3 released are consumed during this phase.
Industrial Biotechnology
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2020
Streptomycin and various other antibiotics are produced using strains of Streptomyces griseus. Spores of this actinomycete are inoculated into a medium to establish a culture with a high mycelial biomass for introduction into an inoculum tank, with subsequent use of the mycelial inoculum to initiate the fermentation process in the production tank. The medium contains soybean meal (N-source), glucose (C-source) and NaCl. The process is carried out at 28°C and the maximum production is achieved at a pH range of 7.6–8.0. High agitation and aeration are needed. The process lasts for about 10 days. The classic fermentation process involves three phases. During the first phase, there is a rapid growth of the microbe with production of mycelial biomass. Proteolytic activity of the microbe releases ammonia (NH3) to the medium from the soybean meal, causing a rise in pH. During this initial fermentation phase, there is little production of streptomycin. During the second phase, there is little additional production of mycelium, but the secondary metabolite, streptomycin, accumulates in the medium. The glucose and NH3 released are consumed during this phase. The pH remains fairly constant—between 7.6 and 8.0. In the third and final phase, when carbohydrates become depleted, streptomycin production ceases and the microbial cells begin to lyse, pH increases, and the process normally ends by this time. After the process is complete, mycelium is separated from the broth by filtration and the antibiotic is recovered. In one method of recovery and purification, streptomycin is adsorbed onto activated charcoal and eluted with acid alcohol. It is then precipitated with acetone and further purified by use of column chromatography.
Antibiotics: The Battle with the Microbes
Published in Richard J. Sundberg, The Chemical Century, 2017
In 1939, Waksman turned his efforts to finding a compound active against tuberculosis. His laboratory investigated many microorganisms using Dubos’ competitive selection approach. The first two active compounds found, actinomycin and streptothricin, were too toxic for application, but during this period Waksman established a collaboration with Merck. One of his graduate students, Albert Schatz, continued searching for microorganisms with antibiotic activity. After screening several hundred, he found an organism, Streptomyces griseus, that produced a substance, called streptomycin, which was active against many microorganisms. It also proved active against tuberculosis bacilli. Waksman did not have facilities for animal tests, but a collaboration was initiated with William Feldman, DVM, and H. Corwin Hinshaw, M. D., Ph. D., of the Mayo Clinic in Rochester MN USA Feldman was an expert in animal TB and Hinshaw was an expert in pulmonary disease. The drug was tested on guinea pigs at the Mayo Clinic in 1944, with promising results. Waksman turned to Merck to produce sufficient material for tests in humans. Merck chemists, led by Karl Folkers and Max Tischler, produced sufficient material. The results were highly promising and led to the first clinically successful drug against TB. Treatment with streptomycin was rapidly adopted, although the drug was very expensive to manufacture. Resistance also began to develop, within months in some patients. Feldman himself became infected, probably through exposure in the course of his laboratory work, but was successfully treated with streptomycin in combination with para-aminosalicylic acid (PAS) (see below). Streptomycin had shown that TB was subject to treatment by antibiotics. Although not the final word, it opened the way to more effective treatments. Selman Waksman received the Nobel Prize in Medicine or Physiology in 1952.
One-pot synthesis and characterization of Schiff base macrocyclic complexes as a potential bioactive core – a review
Published in Journal of Coordination Chemistry, 2021
J. P. Remiya, T. S. Sikha, B. Shyni
Keypour et al. [122] described the synthesis of two new Cd(II) macrocyclic Schiff base complexes [Scheme S24, supplementary material] via metal templated [1 + 1] cyclocondensation of 2,6-pyridinedicarbaldehyde or 2,6-diacetylpyridine with 2,2′-(piperazine-1,4-diylbis(methylene))dianiline. The antibacterial properties of two macrocyclic complexes were studied against four gram-positive (Bacilus anthracis, Bacillus thuringiensis, Bacillus subtilis, Streptomyces griseus) and five gram-negative bacteria (Salmonella enteritidis, Stenotrophomonas maltophilia, Pseudomonas fluorescens, Salmonella typhi, Ralstonia solanacearum) using chlortetracycline and penicillin as standard antibiotics. For antibacterial activity, [CdL1(ClO4)2](CH3CN) and [CdL2(ClO4)2](CH3CN) were more effective against B. subtilis. In certain cases, these compounds were more potent than chlorotetracycline and penicillin. According to the results, the MIC values of the complexes against the bacterial strains ranged from 2 to 8 mg/mL.