Isolation and identification of three new 5-alkenyl-3,3(2H)-furanones from two Streptomyces species using a genomic screening approach

Analyses of biosynthetic gene clusters derived from Streptomyces aculeolatus NRRL 18422 and Streptomyces sp. Eco86 indicated that both microorganisms have similar type I polyketide synthase (PKS) gene Clusters with relatively few genes encoding post-PKS elaborative enzymes. However both gene clusters included a sequence coding for a relatively uncommon oxidative enzyme related to Baeyer-Villiger, flavin-type monooxygenases. Screening of culture extracts for compounds with the predicted physicochemical properties of the end products from these loci, led to the isolation of three 5-alkenyl-3,3(2H)-furanones, one (E-837, 1) from the former and t-wo (E-492, 2 E-975, 3) from the latter strain. The structures, confirmed by spectral analyses including MS, and ID and 2D NMR experiments, were in accord with those predicted by genomic analyses. Baeyer-Villiger type oxidation is postulated to be involved in the formation of the furanone moieties in these molecules. All three new compounds were tested for their electron transport inhibitory activities. They had IC50 values of 1 similar to 4 mu g/ml against Ascaris suum NADH-fumarate reductase and 1 similar to 12 mu g/ml against bovine heart NADH oxidase.