SUMMARY : Sixty Streptomyces isolates which produce polyene antibiotics were isolated from 25 soil samples collected in different parts of the world. Of these isolates 25 produced tetraenes, 23 produced pentaenes, 1 produced a hexaene, and 15 produced heptaenes. One isolate produced simultaneously a tetraene and a pentaene, another produced a tetraene and a heptaene, and a third produced a tetraene, a pentaene and a heptaene. The antibiotics showed activity against a wide range of fungi ; the minimum inhibitory concentrations against Saccharomyces cereuisiae, Aspergillus niger, Mucor racernosus, Candida albicans, Fusarium culmorum and Trichophyton mentagrophytes are given for 10 of them. The distribution of activity between culture filtrate and mycelium is given for 14 of the antibiotics.Hazen & Brown (1951) described the isolation of an antifungal antibiotic (fungicidin) from a Streptomyces sp. It was active against a wide range of yeasts and other fungi, but not against bacteria. The ultraviolet (u.v.) absorption spectrum of the antibiotic in ethanol showed sharp maxima a t 290, 305 and 320 mp.; the frequency differences between these absorption peaks is characteristic of a series of conjugated double bonds, and the chromophoric grouping of the compound is of polyene type. Many other antibiotics of similar properties have been described in recent years in publications from the U.S.A. or Japan, and they may be grouped together on the basis of certain general properties :(1) They inhibit the growth of a wide range of fungi, including yeasts, but are inactive against bacteria.(2) They show a relatively high toxicity when injected into animals, but are much less toxic when given by mouth.(3) They are of low solubility in water but dissolve more readily in aqueous solutions of the lower alcohols, and are easily soluble in aqueous pyridine.
substances besides B,,, Shorb's method of assay greatly facilitated the later stages of the American work.A search for more economic sources of B,, than liver led to the discovery of its presence in the liquors derived from the commercial production of streptomycin by the then established deep-fermentation methods for its large-scale production. It is now generally preferred, however, to carry out separate fermentations for B,, with Streptomyces or some other organism specially selected for its ability to produce B,, free from analogues (see below). This is now the major commercial source of B,,.To the analyst, B,, poses problems ranging from an evaluation of the compound itself to the determination of the almost infinitesimal amounts in sea water. For a proper understanding of these problems, some preliminary consideration of the chemistry of B,, is essential.In the later stages of isolating BIZ from liver and fermentation liquors, it became clear that a number of compounds closely similar in properties to B12, but distinguishable from it by partition chromatography, were present in the original materials or were formed during the extraction processes then in use. These compounds, designated B12a, B12b and BIZc, were later shown to be readily convertible to B,,, when it was realised that cyanide, in addition to co-ordinated tervalent cobalt, formed an essential part of the B,, molecule. The cyanide can be displaced from B,, by photolysis or by certain reagents. Replacement with hydroxyl gives BIza and B12b, subsequently shown to be identical. Replacement with nitrite gives BlZc. These substances, originally isolated from natural sources, may be converted to B,, by treatment with cyanide. The term "cobalamin" was coined to refer to the intact B,, structure without the cyanide group. Hence B,, itself became cyanocobalamin, B12a and BIZb hydroxocobalamin and so on. Other cobalamins may be formed by treatment with different reagents.14 Subsequently it was recognised that another series of compounds, differing more fundamentally from B,,, existed in such materials as fermentation liquors, bovine rumen contents, calf faeces and sewage ,18 J9p20
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