Collaborative Biosynthesis of a Class of Bioactive Azaphilones by Two Separate Gene Clusters Containing Four PKS/NRPSs with Transcriptional Crosstalk in Fungi. (30th January 2020) - Huang, Xuenian
Abstract: Azaphilones are a family of fungal polyketide metabolites with diverse chemical structures and biological activities with a highly oxygenated pyranoquinone bicyclic core. Here, a class of azaphilones possessing a 6/6/6/6 tetracyclic ring system was identified in Aspergillus terreus, and exhibited potential anticancer activities. The gene deletions and biochemical investigations demonstrated that these azaphilones were collaboratively synthesized by two separate clusters containing four core‐enzymes, two nonreducing PKSs, one highly reducing PKS, and one NRPS‐like. More interestingly, we found that the biosynthesis is coordinately regulated by a crosstalk mechanism between these two gene clusters based on three transcriptional factors. This is a meaningful mechanism of fungal secondary metabolism, which allows fungi to synthesize more complex compounds and gain new physiological functions. The results provide a new insight into fungal natural product biosynthesis. Abstract : Zunehmend komplexer : Zwei separate Cluster mit vier Kern‐Genen, die zwei nrPKSs, ein hrPKS sowie ein NRPS‐artiges Enzym kodieren, synthetisieren gemeinsam eine Klasse bioaktiver Azaphilone in Aspergillus terreus . Die Biosynthese wird durch die kollaborative Transkriptionsregulation koordiniert, die auf drei Regulatoren in zwei Clustern basiert.