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Hymeglusin is a fungal β-lactone antibiotic that inhibits HMG-CoA synthase (IC50 = 0.12 μM) by covalently modifying the active Cys129 residue of the enzyme.[1][2] At a dose of 25 mg/kg, hymeglusin inhibits cholesterol biosynthesis in rats by 45%. Chiral studies indicate that the (2R,3R)-β-lactone moiety of hymeglusin is important for eliciting the specific inhibition of HMG-CoA synthase.[3] As a cell-wall targeting antibiotic, hymeglusin has been used to investigate the role of a gene important for controlling S. aureus virulence in a mouse sepsis model of infection.[4].
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