Biosynthesis\nof Tetramate Derivatives in Penicillium crustosum Reveals the Involvement of <i>ortho</i>-Quinone Methide\nin Crosstalk of Multiple Pathways

Genome\nmining and gene deletion experiments in Penicillium\ncrustosum proved the involvement of the PKS-NRPS PemA\nand the <i>trans</i>-enoyl reductase PemB in the formation\nof three enantiomeric clavatol-containing tetramate pairs. Overexpression\nof a transcription factor significantly improved the product yields.\nFeeding experiments provided evidence for their formation via 1,4-Michael\naddition of hydroxyclavatol to two tetramates from the Pem pathway.\nThis study provides another example of the involvement of reactive\nintermediates in multiple biosynthetic pathways.