An Enzyme-Mediated Aza-Michael Addition Is Involved in the Biosynthesis of an Imidazoyl Hybrid Product of Conidiogenone B

Abstract

Meleagrin B is a terpene-alkaloid hybrid natural product that contains both the conidiogenone and meleagrin scaffold. Their derivatives show diverse biological activities. We characterized the biosynthesis of (-)-conidiogenone B (<b>1</b>), which involves a diterpene synthase and a P450 monooxygenase. In addition, an α,β-hydrolase (Con-ABH) was shown to catalyze an aza-Michael addition between <b>1</b> and imidazole to give <i>3S</i>-imidazolyl conidiogenone B (<b>6</b>). Compound <b>6</b> was more potent than <b>1</b> against <i>Staphylococcus aureus</i> strains.