GB692066A - Improvements in or relating to antibiotics and the preparation thereof - Google Patents

Abstract

An antibiotic thiolutin is produced by cultivating in a nutrient medium a strain of Streptomyces albus, the cultural characteristics of which are described, or a mutant thereof. The antibiotic is effective against bacteria and fungi, neutral, slightly soluble in water, contains the elements carbon, hydrogen, oxygen, nitrogen and sulphur, and the mineral oil suspension shows characteristic absorption bands in the infra red region of the spectrum especially at 3295, 3220, 3110, 1680, 1645, 1607, 1551, 1439, 1322, 1239, 1138, 1091, 1060, 1039, 975, 875, 825, 800, 740, 729. The ultra-violet absorption spectrum is characteristic. It is soluble in organic solvents such as butanol, methanol, ethanol, acetone, methyl isobutyl ketone, glacial acetic acid, dimethylformamide, chloroform, pyridine and isopropanol; less so in petroleum ether, benzene and hexane. The antibiotic is produced by growing the micro organism in a nutrient medium containing (a) carbohydrate, e.g. sugars, starch and glycerol, (b) organic nitrogen source, e.g. soybean meal, cotton seed meal, peanut meal, corn steep liquor and N-Z-Amine B (enzymatic digest of casein), (c) mineral salts, e.g. sodium chloride, sodium nitrate, magnesium sulphate and potassium phosphate, (d) buffer, e.g. calcium carbonate and potassium dihydrogen phosphate, (e) antifoaming agent, e.g. vegetable or animal oil. The pH is adjusted to 6 to 7, the temperature is 23 DEG to 32 DEG C., and preferably 26 DEG to 30 DEG C., the duration of treatment 2 to 7 days with agitation and aeration at the rate of 1/2 to 2 volumes air per volume of broth per minute. The antibiotic is recovered from the clarified broth by (a) solvent extraction with water-immiscible organic solvents at acid, neutral or basic pH, but preferably at acid or neutral pH. Alcohols, esters, ketones, hydrocarbons, ethers and chlorinated solvents may be used, and in particular butanol, ethyl acetate, methyl isobutyl ketone, benzene and chloroform; (b) absorption on, e.g. activated carbon followed by elution with a solvent. The broth is clarified by driect filtration with a filler aid, or after acidification to preferably pH2 and heating to 70-90 DEG C. for 10 to 60 minutes. The antibiotic may be crystallized from solvents such as alcohols, e.g. methyl alcohol, ketones, dimethylformamide or mixtures thereof with water. Suspensions of the antibiotic in peanut oil or sesame oil when injected into mice were less toxic than when the antibiotic was taken by mouth.