Patent GB-828921-A (GB)
Title: Process for fermentative manufacture of combined agricultural vitamin b-antibiotic preparations
IPC: A23K20/195
Filed: 1956-05-08
Abstract: A Vitamin B12 antibiotic preparation suitable for agricultural use particularly as an animal feed supplement is prepared by conjointly cultivating a Vitamin B12-producing-microorganism with a tetracycline antibiotic-producing-micro-organism in an aqueous nutrient medium under aerobic conditions.  Examples relate to the preparation of (a) Vitamin B12 chlortetracycline mixture by conjointly cultivating Streptomyces olivaceus or a Nocardia sp. producing Vitamin B12 with a chlortetracyclic-producing strain of S. aureofaciens, and (b) Vitamin B12 oxytetracycline mixture by conjointly cultivating S. olivaceus with S. rimosus.  Glucose is essential for the growth of the Vitamin B12-producing-micro-organism and sucrose for the growth of the chlortetracycline or oxytetracycline - producing - microorganism and vegative inocula of these microorganisms are prepared in nutrient media containing the respective essential sugars.  In one example, nutrient media of pH 6.9 and containing 0.25% glucose, 2.5% sucrose, soymeal, CaCO3, NaCl, (NH4)2SO4, molasses, corn steep solids and cobalt chloride is inoculated first with one and then with another of the above vegetative cultures, fermented for 60 hours at 28 DEG  C., filtered and the mycelium dried and powdered to yield the desired chlortetracycline Vitamin B12 preparation.  In another example, a similar medium containing glucose alone was inoculated in a similar manner and fermented 30 hours with rapid growth of the S. olivaceus and depletion of the glucose, sucrose was then added and the fermentation continued during which time the growth of S. aureofaciens was rapid and that of the S. olivaceus was stationary. In another example, a similar medium containing glucose and in addition chlortetracycline and actidione was fermented 30 hours with S. olivaceus, sucrose added and then S. aureofaciens and the fermentation continued.  In the case of the Vitamin B12 oxytetracycline, the oxytetracycline - producing - micro-organism requires starch and the medium which is inoculated with the two micro-organisms contains, inter alia, glucose 1.5% and starch 1.5% The broth is filtered and the mycelium dried and powdered to produce an animal feed (see Group I).  Specifications 687,661 and 730,919 are referred to.ALSO:An animal feed supplement containing vitamin B12 and a tetracycline antibiotic is prepared by conjointly cultivating a vitamin B12 - producing micro organism, e.g. streptomyces olivaceus with a tetracycline-producing micro organism, e.g. streptomyces aureofaciens (chlortetracycline) or streptomyces rimosus (oxytetracycline), in an aqueous medium under aerobic conditions. Optimum production is obtained by inoculating a nutrient medium containing, inter alia, glucose, and then adding sucrose when the glucose has been utilised, the glucose favouring the development of the vitamin B12 microorganism and the sucrose the antibiotic producing micro organism (see group IV(b)).  The broth is filtered and the mycelium dried and powdered to produce the animal feed supplement.  Specifications 687,661 and 730,919 are referred to.