Genome-based analysis of the type II PKS biosynthesis pathway of xanthones in Streptomyces caelestis and their antifungal activity

The ethyl acetate extract from the liquid fermentation of S. caelestis Aw99c exhibited high and broad antifungal activities against plant pathogenic fungi. Bioassay guide fractionation led to the discovery of two xanthones, citreamicin ε and θ. The draft genome sequence of S. caelestis Aw99c was analyzed by a similarity-based approach to elucidate the pathway for the citreamicins. A 48 kb citreamicin (cit) gene cluster with 51 open reading frames encoding type II polyketide synthases and unique polyketide tailoring enzymes was proposed based on the genome analysis and the chemical structure derivation. In vitro antifungal assay showed that citreamicin ε exhibited significant growth inhibition against the plant pathogenic fungi with MIC values ranging from 1.56 to 12.5 μM. The cellular structural change of M. grisea treated with citreamicin ε was detected by SEM and the result showed that citreamicin ε caused disruptive surface of the mycelia.