Collaborative Biosynthesis of a Class of Bioactive Azaphilones by Two Separate Gene Clusters Containing Four PKS/NRPSs with Transcriptional Crosstalk in Fungi.

Collaborative Biosynthesis of a Class of Bioactive Azaphilones by Two Separate Gene Clusters Containing Four PKS/NRPSs with Transcriptional Crosstalk in Fungi.

Angew Chem Int Ed Engl. 2020 Jan 06;:

Authors: Huang X, Zhang W, Tang S, Wei S, Lu X

Abstract
Azaphilones are a family of fungal polyketide metabolites with diverse chemical structures and biological activities possessing a highly oxygenated pyranoquinone bicyclic core. Here, a class of azaphilones possessing a 6/6/6/6 tetracyclic ring system were 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 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.

PMID: 31908094 [PubMed – as supplied by publisher]

Source: Industry