Cofactor F₄₂₀, an emerging redox power in biosynthesis of secondary metabolites

Cofactor F₄₂₀ is a low-potential hydride-transfer deazaflavin that mediates important oxidoreductive reactions in the primary metabolism of archaea and a wide range of bacteria. Over the past decade, biochemical studies have demonstrated another essential role for F₄₂₀ in the biosynthesis of various classes of natural products. These studies have substantiated reports predating the structural determination of F₄₂₀ that suggested a potential role for F₄₂₀ in the biosynthesis of several antibiotics produced by Streptomyces. In this article, we focus on this exciting and emerging role of F₄₂₀ in catalyzing the oxidoreductive transformation of various imine, ketone and enoate moieties in secondary metabolites. Given the extensive and increasing availability of genomic and metagenomic data, these F₄₂₀-dependent transformations may lead to the discovery of novel secondary metabolites, providing an invaluable and untapped resource in various biotechnological applications.