In efforts to identify agents active against a panel of nosocomial pathogens, our attention was directed toward a Penicillium sp. that demonstrated activity against methicillin-resistant Staphylococcus aureus (MRSA). Large scale liquid fermentation of the producing organism, followed by ethanol extraction of the mycelial mass, solvent partitioning, LH-20 chromatography, and reverse phase high-performance liquid chromatography, yielded the known compound isochromophilone VI (2) and the novel compound isochromophilone IX (3) as red glasses. Isochromophilone VI (2) was identified by comparison of spectroscopic data with literature. Electrospray mass spectroscopy, high-resolution mass measurement, 1H and 13C NMR (APT, COSY, HMBC) analysis, and comparison of 13C NMR data with isochromophilone VI (2) allowed the structural elucidation of isochromophilone IX (3). Isochromophilone IX (3) displays a specific rotation [α]D +430° (c 0.10 in MeOH), with the same sign as isochromophilone VI (2), suggesting it is biosynthetically derived from the same sclerotiorin isomer and possesses identical stereochemistry (tentatively assigned as 7R,13S). In conclusion, isochromophilone IX (3) has been identified as a novel antibiotic active component (minimum inhibitory concentration (MIC) 50µg mL−1 against MRSA) from a Penicillium species (Accession No. MINAP9902) and represents the first occurrence of an γ-amino butyric acid (GABA) containing metabolite among only four naturally occurring members of this structure class.