From Genes to Molecules: The <i>Fusarium</i> PKS16 Gene Cluster Facilitates the Biosynthesis of Proliferapyrones

Ascomycete fungi of the genus Fusarium are found in manifold ecological niches and thus pursue several lifestyles. On average, individual Fusarium species have the genetic capability to produce 50 natural products (NPs), which are in general thought to improve the fungus's fitness in defined environments. This also includes NPs with toxic potential (mycotoxins) contaminating food and feed sources. Recent research has shown that the production of NPs is tightly regulated on the transcriptional level and depends on the delicate balance between the deposition and removal of histone marks. Within this study, we show that the expression of the prior cryptic Fusarium PKS16 biosynthetic gene cluster (BGC) greatly depends on modifications at histone H3 lysine 27 (H3K27). By combining molecular-, chemical-, and bioinformatic analyses we show that the PKS16 BGC from F. fujikuroi B14 (FfB14) consists of nine genes, including a positively acting pathway-specific transcription factor, which although absent in some fusaria, functions in activating other PKS16 cluster genes. Moreover, we linked the PKS16 BGC to the biosynthesis of proliferapyrone (PRO) E, an isomer of the recently isolated PRO A.