Sclerotiorin, a novel inhibitor of lipoxygenase from Penicillium frequentans.

Foods rich with unsaturated fatty acids are prone to enzymatic and nonenzymatic lipid peroxidation; lipoxygenase, a metalloenzyme and a free radical former, oxidizes polyunsaturated fatty acids and is one of the key enzymes in lipid oxidation. Here, we report sclerotiorin, purified from the fermented broth of Penicillium frequentans, as a potent reversible, uncompetitive inhibitor against soybean lipoxygenase-1 (LOX-1) with a half-maximal value (IC50) of 4.2 microM. The inhibitor also showed an antioxidant property by scavenging free radical with an ED50 of 0.12 microM; in addition, nonenzymatic lipid peroxidation was inhibited with a PD50 value of 64 microM and did not show metal chelation. The observations made in this study suggest that sclerotiorin possibly inhibits LOX in two ways: one, by interacting with the enzyme-substrate complex, and two, as an antioxidant by quenching or trapping the free radical intermediates formed in the enzyme reaction. Sclerotiorin compares well with other known natural and synthetic lipoxygenase inhibitors.