Abstract
Conventional heme enzymes utilize iron-oxygen intermediates to activate substrates and drive reactions. Recently, Chen et al. discovered a novel NADPH-independent superoxide mechanism of heme catalase EasC, which facilitates an O(2)-dependent radical oxidative cyclization reaction during ergot alkaloid biosynthesis. This enzyme coordinates superoxide-mediated catalysis by connecting spatially distinct NADPH-binding pocket and heme pocket via a slender tunnel, offering a novel perspective on the catalytic mechanisms of heme enzymes in nature.