During our continuing search for new biologically active metabolites from myxobacteria, a new screening system using an MT-4 cell culture assay with HIV-1 led to the discovery of the novel secondary metabolite, phenoxan (Fig. 1). It was isolated from an acetone-extract of the cell mass of Polyangium spec, strain PI VO19 and purified as described elsewhere. The chemical and spectroscopic structure elucidation revealed phenoxan to be a new substituted oxazole-γ-pyrone showing a structural similarity to the microbial metabolites aureothin and spectinabilin. The cytotoxicity of phenoxan for different human lymphoblastoid cell lines in vitro and its suppression of HIV-1 infection in the MT-4 cell culture assay has been described. In this paper we wish to report on the production of phenoxan, its antimicrobial activity, and on experiments with beef heart submitochondrial particles showing that phenoxan is a powerful inhibitor of the eukaryotic respiratory chain at the site of complex I, i.e., NADH: ubiquinone oxidoreductase.