Descubrimiento de un Clúster Fúngico HR-PKS que Codifica Vías Biosintéticas para Macrólidos con Dos Tamaños de Anillo...

Through the heterologous expression of a highly reducing polyketide synthase and a thioesterase from the apeml cluster, a putative macrolide biosynthetic gene cluster on the genome of Aspergillus petrakii, we obtained a naturally new 10-membered macrolide (1) and recifeiolide (2), a known 12-membered macrolide. To obtain modified macrolides, feeding experiments using Aspergillus oryzae transformants expressing individual modification enzymes were employed, resulting in the isolation of aspinolide A (3) and 2 new macrolides, petrakilides A (4) and B (5). These findings highlight a promiscuous enzymatic cascade capable of generating macrolides with distinct scaffolds and different ring sizes.