Crisamicin C, a new isochromanequinone antibiotic. Isolation, structure determination, and biosynthesis

Micromonospora purpureochromogenes subsp. halotolerans was found to produce crisamicin C, a novel antibiotic, together with crisamicin A. Crisamicin C was purified by silica gel column chromatography and its physico-chemical properties, structure and biosynthesis were studied. Crisamicin C, mp 260 degrees C (dec), showed UV maxima at 392 (epsilon 9,497), 261 (epsilon 32,959) and 232 nm (epsilon 24,623) in CH3CN, and gave an IR spectrum with absorbances at 1782 (lactone), 1705 and 1655 (quinone) cm-1. Crisamicin C plasma desorption mass spectrometry (PD-MS) m/z 615.9 [M + H)+, hydroquinone) was 16 amu higher than crisamicin A PD-MS m/z 600 [M + H)+, hydroquinone) suggesting that the two antibiotics differ by one additional oxygen in crisamicin C. Analysis of 1H and 13C NMR spectra, in comparison with those of crisamicin A, indicated that crisamicin C was the 4'a, 10'a epoxide derivative of crisamicin A. Carbon-thirteen labeled acetate feeding experiments were used to confirm the positions of the epoxide and other structural features. Crisamicin C was a more potent antibiotic than crisamicin A, but shared the same spectrum of antimicrobial activity (Gram-positive only).