New antibiotics, pyrrolomycins F1, F2a, F2b and F3 were produced by Actinosporangiu m vitaminophilum sp. nov. when bromide ion was added to the fermentation medium. Addition of other halide ions such as chloride, iodide and fluoride ion showed no effect on pyrrolomycin production, affording polychlorinated pyrrolomycins A, B, C, D and E, but no F components. All four new antibiotics contain 2-4 mol of bromine, and their substitutional position was determined by X-ray analysis and synthesis, supported by spectroscopic analysis. They are strongly active against Gram-positive bacteria and fungi.
Effect of Halide Ions on the Production of PM ComponentsPM antibiotics produced in the fermentation broth were analyzed by means of HPLC. Fig. 1A illustrates a chromatographic pattern of the cultured broth of Actinosporangium vitaminophilum sp. nov. without addition of halide ions. PM-A, E, B, D and C are eluted in that order with C predominating. When 0.1 % of NaBr was added in the culture medium, none of these PMs were detected in HPLC.Instead, peaks due to PM-F1, F2a, F2b and F3 appeared (Fig. I B). The relative ratio of each PM-F components depended on the amount of NaBr added. As the amount of NaBr was increased from 0.05 % to 0.1 % and 0.2 %, the relative ratio of PM-F1, substituted with four bromine atoms, was markedly increased, while PM-F, substituted with two atoms of bromine and two atoms of chlorine was decreased. PM-F20, and PM-F,, which contained three atoms of bromine and one atom of chlorine were less sensitive to the added NaBr. In contrast, when other halogen ions (Cl, I or F) were added, the HPLC pattern was little changed, and was similar to that of the control fermentation (Fig. 1A).