Production of antibacterial compounds by a Steely hybrid polyketide synthase in Dictyostelium.

Abstract

Ecological interactions in the soil are often mediated by small molecules, which can later become valuable drugs. The cellular slime mould Dictyostelium discoideum is a soil microbe with a life cycle consisting of unicellular (amoeba) and multicellular phases (fruiting bodies). After Dictyostelium amoebae have consumed all available bacteria, they form stalked fruiting bodies to aid dispersal of the spores. The dying stalk cells repurpose a hybrid polyketide synthase to make abundant chlorinated metabolites, which persist in their fruiting bodies. The most abundant of the chlorinated metabolites, CDF-1, is a chlorinated dibenzofuran, which was shown to be an effective antimicrobial, being roughly as potent as ampicillin. Here, we identify CDF-2 and -3 by purification, followed by MS and NMR, after increasing their yields by using producer species and growth condition optimisation. Similar to CDF-1, CDF-2 and -3 are chlorinated dibenzofurans and exhibit more potent antibacterial activity against Gram-positive bacteria than ampicillin. We propose that the ecological function of CDF-2 and -3 is to protect the dormant spores from degradative bacteria.