Antibiotics, from Bacillus brevis

Structure of a Peptide Antibiotic from Bacillus brevis Extracts from the bacterium Bacillus brevis contain a peptide with antibiotic properties. This peptide forms complexes with metal ions and apparently disrupts ion transport across the cell membranes of other bacterial species, killing them. The structure of the peptide has been determined from the following observations. 

Tyr substructures are, moreover, found within several peptidic antibiotics, for example the edeines 57 from Bacillus brevis, or within cyclodepsipeptides that have been isolated from marine sponges, for example jaspamides A-C 59 [106] or geo-diamolides H-I 58 [107] (Scheme 1.5.9). The chondramides 60 are closely related antibiotics that have been obtained from the myxobacterium Chondromyces croca-tus. Within the edeine biosynthesis D-/ -Tyr 9 seems to be a real precursor [89]. The biosynthesis of the jaspamides, the geodiamolides, or the chondramides has not yet been investigated. 

Among the peptide antibiotics are gramicidin S (from Bacillus brevis) and bacitracin A (from Bacillus subtilis), which contain D-amino acids in addition to l-amino acids ... 

Marahiel MA, Zuber P, Czekay C, Losick R. Identification of the promoter foi a peptide antibiotic gene from Bacillus brevis and studies on its regulation in Bodllus subiilis. ] Bacteriol 1987 169 2215-2222. 

Nozaki S, Muramatsu 1. Natural homologs of gramicidin S. J Antibiot 1987 37 689-690. Thibault P. Faubert D, Kaiunanirhy S, Boyd RK. Holmes CFB. Isolation, mass spectromctric characterization, and protein phosphatase inhibition properties of cyclic peptide analogs ol gramicidin S from Bacillus brevis (Nagano strain). Biol Mass Spectiom 1992 21 367—379. 

Biosynthesis of (S)-/ -Tyrosine in Bacillus brevis Vm4 //-Tyrosine 43 is a constituent of the peptide antibiotics edeine A and B [60] obtained from cultures of BaciUus brevis Vm4. //-Tyrosine is derived from a-tyrosine 42 by use of a tyrosine 2,3-aminomutase [61]. The purified enzyme has properties fundamentally different from those of all other aminomutases so far mentioned. It requires ATP and Mg2+ ions, but no other cofactors. 

To date, the most extensively studied natural ionophore is gramicidin,10 a polypeptide antibiotic isolated from the bacterium Bacillus brevis. Indeed, the idea of a channel-like structure for ion transport was inferred from its study. However, unlike channel proteins, which are exclusively composed of L-amino acids, each alternate amino acid in gramicidin has D-stereochemistry. It is composed of 16 residues, 15 of which are amino acids. The structure is summarized below, in which Xxx has the following identities gramicidin A (gA), Trp gB, Phe gC, Tyr gD, a mixture of gA, gB, gC, -80 5 15. 

The isolation of the antibacterial antibiotic tyrtxridin from itie soil hacterium Bacillus brevis by Dubois suggested the Ftnbahle existence of many antibiotic subslance.s in nature jnd provided Ihe impetus for the search for them. An organ-... 

In 1939 Dubos reported the isolation of the antibiotic tyrothricin from culture filtrates of strains of Bacillus brevis > < He and his co-workers soon succeeded in separating tyrothricin with organic solvents into two crystalline compounds, the neutral gramicidin and the basic tyrocidine (formerly called graminic acid and gramidinic acid). Tyrothricin is thus a term for the partially purified antibiotic obtained from the culture fluids of Bacillus brevis. It contains on the average a mixture of 20 per cent gramicidin and 80 per cent tyrocidine. Besides these, at least three further polypeptides have been found by countercurrent distribution of tyrothricin. 

Tyrocidins homodetic, homomeiic, cyclic peptide antibiotics active against Gram-positive bacteria. Like the Gramicidins (see), X are produced by Bacillus brevis. Hie structure of tyrocidin A, confirmed by total synthesis, is cyclo-(-Val-Om-Leu-D-Phe-Pro-Phe-D-Phe-Asn-Gln-IJr-). In tyrocidin B, Phe is replaced by Trp. In tyrocidin C, Phe is replaced by Tip, D-Phc7 by D-Hp, and Asng by Asp. Tyrocidin E differs from tyrocidin A by replacement of Asn by Asp, and Tyrio by Phe. 

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