Aureusimine B, also known as phevalin, is a natural pyrazinone produced by certain fungi and by Staphylococcus spp., including S. aureus. Its synthesis appears to be initiated by a conserved nonribosomal peptide synthetase that creates a dipeptide (phenylalanine-valine) aldehyde, which then undergoes cyclization and oxidation. Aureusimine B inhibits calpain in a casein hydrolysis assay (IC50 = 1.3 μM), contributes to S. aureus infection in mice, and alters human keratinocyte gene expression.