Pyrrolomycins F1,F2a,F2b and F3,new metabolites produced by the addition of bromide to the fermentation.

Abstract

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).

Observations on the Remarkable (and Mysterious) Wound-Healing Process of the Bottlenose Dolphin

“…Although the origin of these non-human-derived compounds has not been identified, several resemble known substances that are produced by marine organisms, such as algae and plankton (Gribble, 2003). Organohalogens are known to exhibit antimicrobial properties, such as the inhibition of biofilm formation (Janssens et al, 2008) and antibiotic activity (Ezaki et al, 1983). One might imagine that under certain circumstances, for example, as the blubber tissue undergoes ''decomposition'' following trauma, some of these compounds could be released locally and could provide antimicrobial protection to the tissues within the immediate wound environment.…”

Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

“…Pyrrolomycins F1, F2a, F2b and F3 ( Figure 4) were isolated from Actinosporangium vitaminophilum sp. nov. when bromide ions were added to the culture medium [42].…”

Synthesis and anti‐staphylococcal activity of new halogenated pyrroles related to Pyrrolomycins F

“…PM-D and vancomycin were used for comparative purposes and quality control of the methods. MICs against bacterial strains were determined using the broth dilution micro-method as described [6]. 4.42 g (20 mmoles) of 3,5-dichloro-2-methoxybenzoic acid, commercially available, and 15 ml (24.50 g, 200 mmoles) of thionyl chloride were refluxed until the generation of hydrochloric acid ceased (approximately 8 hours).…”

“…Some PM-F components possessed equal or more potent activity, against some Gram-positive bacteria, than PM-D, the most active component among PM-A to E [6]. We have previously described the synthesis of some brominated pyrrolomycin analogs [7] and their activity against antibiotic sensitive and resistant S. aureus clinical strains [8].…”

“…A different group of pyrrolomycins, generically named PM-F, has been produced from A. vitaminophilum SF-2080 when bromide ion was added to the fermentation medium [6] (Figure 2). Some PM-F components possessed equal or more potent activity, against some Gram-positive bacteria, than PM-D, the most active component among PM-A to E [6].…”