Colabomycin A

The structure of colabomycin A (1) was elucidated by a detailed spectroscopic analysis. Two-dimensional NMR spectroscopy experiments provided assignments of the proton and carbon resonances of the tetraene carboxamide chains occurring in 1. The configurations of eight out of nine double bonds were determined by analysis of their coupling constants. The absolute configurations of C-4 (4S), C-5 (5R) and C-6 (6S) were established from the CD spectra of the parent compound and of 2-(6-oxo-2,4-hexadienoylamino)-5,6-epoxy-1,4-benzoquinone (2), which was obtained from 1 by mild chromic acid oxidation.

The yellow colabomycins A to C, three new antibiotics of the manumycin group produced by Streptomyces griseoflavus (strain Tü 2880), were detected by chemical screening. They were isolated from mycelium extracts by column chromatography on various adsorbents, followed by preparative reversed phase HPLC. The main compound, colabomycin A (1), was characterized and shown to be chiefly biologically active against Gram-positive bacteria and stem cells of murine L1210 leukemia.

The influence of enhanced O2 concentration on growth and formation of secondary metabolites by Streptomyces griseoflavus (strain Tü 2880) was investigated in a stirred tank and in an air-lift fermentor. At a partial pressure of O2 Po2 = 1880 mbar the growth was lowered by 50% compared to Po2 = 210 mbar, whilst substrate consumption and O2 uptake rate increased markedly. Production of the colabomycin complex reached maximum values at Po2 = 630 mbar. A similar increase of secondary metabolite formation was obtained when glycerol or acetate were fed at Po2 = 220 mbar. The portion of the derivate colabomycin A in the product mixture rose from 43% at Po2 = 210 mbar to 73% at Po2 = 1260 mbar. Since dissolved O2 concentration has a significant influence on productivity and selectivity it may be used to regulate aerobic fermentation processes.