In efforts to identify agents active against nosocomial pathogens, a Penicillium sp. demonstrating activity against methicillin-resistant Staphylococcus aureus (MRSA) was studied. Large-scale liquid fermentation (10 L potato dextrose broth) of the organism yielded a mycelial mass; its ethanol extract showed antibiotic activity. Solvent partitioning, LH-20 chromatography (MeOH/H₂O 9:1), and reverse phase high-performance liquid chromatography (octadecylsilane, CH₃OH/H₂O with 0.1% CF₃CO₂H) isolated the known isochromophilone VI (6.0 mg) and a novel compound isochromophilone IX (8.1 mg) as red glasses. Isochromophilone IX's molecular formula C₂₅H₃₀NO₆Cl was established via electrospray mass spectroscopy and high-resolution mass measurement. ¹³C attached proton test, ¹H NMR, ¹H−¹H correlated spectroscopy, and heteronuclear multiple-bond connectivities analyses, along with comparison to isochromophilone VI, elucidated its structure. Specific rotation ([α]ᴅ +430° in MeOH, same sign as isochromophilone VI's +128°) suggested biosynthetic derivation from the same sclerotiorin isomer, tentatively assigning 7R,13S stereochemistry. Isochromophilone IX represents the first naturally occurring γ-amino butyric acid (GABA)-containing metabolite among only four naturally occurring members of this structure class reported prior, and exhibits anti-MRSA activity with a minimum inhibitory concentration (MIC) of 50µg mL⁻¹.