The fermentation, isolation and characterization of macromolecular peptide antibiotics: AN-7A, -7B and -7D

A group of new macromolecular peptide antibiotics, named AN-7, was isolated from the culture broth of Streptomyces griseoincarnatus AJ9424. AN-7 was fractionated into three different components, A, B and D. From 18 liters of culture broth (78 units/ml), 10 mg of AN-7A with a specific activity of 2,053 units/mg, 9 mg of AN-7B (1,167 units/mg) and 11 mg of AN-7D (6,225 units/mg) were obtained. All of these samples gave single bands on polyacrylamide gel electrophoresis. They are acidic polypeptides with molecular weights ranging from 12,400 to 13,000. Their UV absorption spectra showed maxima peaks at 280 nm and shoulders at 290 nm. Each AN-7 component has a nonprotein chromophoric component. AN-7A, -7B and -7D have no antibacterial activity against the Gram-negative bacteria tested but strongly inhibit the growth of Gram-positive bacteria and Escherichia coli MP2, a macromolecule permeable mutant strain. The AN-7 components are mutagenic. These antibiotics inhibit the in vitro growth of L1210 cells (ED50 0.13 approximately 0.18 micrograms/ml). AN-7A, -7B and -7D also inhibit the growth of L1210 cells in mice.