Streptomycin fermentation

Streptomycin B (mannosidostreptomycin) has a mannose molecule attached to the methylglucosamine group, and is the first antibacterial product made, but is enzymatically converted to streptomycin later in the fermentation. 

Antibiotics. Solvent extraction is an important step in the recovery of many antibiotics (qv) such as penicillin [1406-05-9] streptomycin [57-92-17, novobiocin [303-81-1J, bacitracin [1405-87-4] erythromycin, and the cephalosporins. A good example is in the manufacture of penicillin (242) by a batchwise fermentation. Amyl acetate [628-63-7] or -butyl acetate [123-86-4] is used as the extraction solvent for the filtered fermentation broth. The penicillin is first extracted into the solvent from the broth at pH 2.0 to 2.5 and the extract treated with a buffet solution (pH 6) to obtain a penicillin-rich solution. Then the pH is again lowered and the penicillin is re-extracted into the solvent to yield a pure concentrated solution. Because penicillin degrades rapidly at low pH, it is necessary to perform the initial extraction as rapidly as possible for this reason centrifugal extractors are generally used. 

Pharmaceutical. Ion-exchange resins are useful in both the production of pharmaceuticals (qv) and the oral adrninistration of medicine (32). Antibiotics (qv), such as streptomycin [57-92-17, neomycin [1404-04-2] (33), and cephalosporin C [61-24-5] (34), which are produced by fermentation, are recovered, concentrated, and purified by adsorption on ion-exchange resins, or polymeric adsorbents. Impurities are removed from other types of pharmaceutical products in a similar manner. Resins serve as catalysts in the manufacture of intermediate chemicals. 

Dihydrostreptomycin sulfate may be prepared from streptomycin sulfate by catalytic hydrogenation (Merck, Pfizer, Cyanamid), electrolytic reduction (Schenley, Olin Mathieson), or by sodium boro hydride reduction (Bristol), or by isolation from a fermentation process (Takeda). 

Fluidised beds have been used previously for the industrial-scale recovery of the antibiotics streptomycin and novobiocin.30 However, more recently, considerable interest has been shown in the use of fluidised beds for the direct extraction of proteins from whole fermentation broths.31 In a packed bed, the adsorbent particles are packed within the contactor. The voidage, that is, the inter-particle space, is minimal and thus feedstock clarification is mandatory to avoid clogging of the bed. In a fluidised/expanded bed, the adsorbent bed is allowed to expand by irrigation with feedstock. Bed voidage is increased, allowing the passage of particulates in the feed. The diameters of the adsorbent beads are exaggerated for illustrative clarity. 

Recovery of valuable products from penicillin, riboflavin, streptomycin, and vitamin B12 fermentation has been recommended as a viable waste control strategy when incorporated into animal feeds or supplements. Penicillin wastes, when recovered for animal feed, are reported to contain valuable growth factors, mycelium, and likewise evaporated spray-dried soluble matter [31,32,34]. 

Little or no loss of antimicrobial activity was further observed after fermentation of raw sausages containing streptomycin (6). However, smoking/scalding processes could cause a 32-45% reduction of the streptomycin activity (7). When semi- or fully preserved sausages were heated at 90-95 C for 1 h, the microbiological activity of the contained streptomycin exhibited a 50% reduction of the initial dose (8) however, some of the initial activity could be demonstrated in the juices exuded from the heated sausages even when the temperature was raised to 120-125 C. 

Spent liquors from streptomycin and other antibiotic fermentations contain appreciable amounts of vitamin B12. Bacterial strains producing high amounts have been specially selected for commercial production. Today vitamin B 2 is obtained from fermentations using selected strains of Propionibacterium or Pseudomonas cultures. A full chemical synthesis process for vitamin B 2 is known. However, it requires some 70 steps and for all practical purposes is of little value. 

Paromomycin Sulfate, USP. The isolation of paromomycin (Humatin) was reported in I9S6 from a fermentation with a Streptomyces sp. (PD 04998), a strain said to resemble 5. rimostis very closely. The parent organism had been obtained from soil samples collected in Colombia. Paromomycin. however, more closely re.sembles neomycin and streptomycin in antibiotic activity than it dtx s oxytetracycline, die antibiotic obtained from S. rintosus. 

Derivation From Streptomyces griseus by aerobic fermentation. The streptomycin is then concentrated by adsorption on activated carbon and purified. 

Ashimycins A and B are two streptomycin analogs (modified in the L-glucos-amine unit) isolated from the fermentation broth of S. griseus [84]. Ashimycin A (compound 79 see pg. 319) carries a glycosidically linked sugar moiety having an... 

The site most often exploited for streptomycin modification is the 3 aldehyde moiety of ring II, the streptose ring. The first semisynthetic analog of streptomycin, dihydrostreptomycin, contained an alcohol in place of the streptose aldehyde (43). This analog was later isolated from fermentation sources (Streptomyces/iM/nidws) (44). Figure 6.2b illustrates many of the aldehyde conversions... 

There is always a need for streamlining the initial purification steps of products that are derived from fermentation. Recent advances in a technique called expanded-bed adsoiption have shown the ability to elimmate the solid-4iquid separation step and thereby increase product yield and reduce processing time. Expanded-bed adsorption is not a new concept, since there are reported applications for streptomycin (23) in the 1950s and novobiocin (24) in the 1970s. However, these applications used adsorbents that were not specifically designed for expanded-bed-adsorption procedures and often required compli-... 

Soybean oil was used as an antifoam agent in aerated fermentations such as productions of penicillin, streptomycin, and tetracycline. It also markedly increases the yield of antibiotics, presumably by providing important nutrients (Smith Thompson, 1989). Soybean oil also was observed to delay the onset of blooms on fruit trees, reducing susceptibility to frost damage. 

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