| 摘要 |
1363075 Enzyme inhibitor BEECHAM GROUP Ltd 13 Sept 1971 [17 Sept 1970 (2)] 44365/70 and 44366/70 Heading C3H [Also in Division A5] The invention relates to the enzyme inhibitor designated MM 4550 and non-toxic salts thereof which inhibitor is an acidic solid with no characteristic ultra violet spectrum and having, when in the form of its barium salt the infra red absorption spectrum shown in the accompanying drawing and which is capable of inhibiting the penicillin-degrading and cephalosporin-degrading action of #-lactamase enzymes derived from strains of Escherichia coli, Klebsiella aerogenes, Proteus vulgaris, Bacillus cereus, Staphylococcus aureus, and Staphylococcus pyogenes. The MM 4550 is produced by cultivation of a MM 4550 producing strain of Streptomyces olivaceous, e.g. ATCC 21379, ATCC 21380, ATCC 21381, or ATCC 21382, or a mutant strain thereof in a nutrient medium containing assimilable sources of carbon, nitrogen and mineral salts, and thereafter recovering MM 4550 from the mixture. The cultivation is preferably carried out aerobically at 20-35‹ C., in a nutrient medium at approximately pH 7. The nutrient medium may contain yeast extract, soyabean flour, meat extract, cottonseed flour, malt, amino acids, distillers dried solubles, protein hydrolysates, and inorganic nitrogen in the form of ammonium or nitrate ions. Suitable carbon sources are glucose, lactose, maltose, starch and glycerol. The MM 4550 may be recovered from the medium by ion-exchange methods, chromatography or gel filtration. The yield may be increased by the inclusion in the growth medium of manganese sulphate, cobalt chloride or calcium carbonate. Antibacterial synergism between MM 4550 and penicillins or cephalosporins has been observed.
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