Collinone, a new recombinant angular polyketide antibiotic made by an engineered Streptomyces strain

Large chromosomal DNA fragments containing different parts of the putative rubromycin polyketide synthase gene cluster were cloned and functionally ex pressed in S. coelicolor CH999. Expression of these clones yielded 5 simila r to 10 metabolites that were not detected in S. collinus culture extracts. This paper focusses on one of the new metabolites, termed collinone, that was isolated in large quantities and purified for spectroscopic structure d etermination and biological screening assays. Collinone is a heavily oxidiz ed angular hexacyclic compound containing an unusual 1,4,5,8(2H,3H)-anthrac enetetrone moiety previously only reported to be present in antibiotics SF2 446A1, A2, A3, B1 and B2 isolated from Streptomyces sp. SF2446. Structure a nalysis of collinone indicates a tridecaketide with a 26 carbon backbone. T he basic benz[a]naphthacene ring system of collinone is angular, similar to the aglycones of the well-known angucycline and angucyclinone antibiotics. While collinone showed antibacterial activity against vancomycin-resistant enterococci. no antifungal or significant antiviral activities were detect ed. Collinone could be a good starting point to obtain new bioactive angucy clin(on)e-like compounds by further genetic engineering of its pathway.