Development of Genetic Dereplication Strains in Aspergillus nidulans Results in the Discovery of Aspercryptin.

Author: 

Chiang YM1,2, Ahuja M3,4, Oakley CE3, Entwistle R3, Asokan A5, Zutz C6, Wang CC1,7, Oakley BR8.
Angew Chem Int Ed Engl. 2015 Nov 13.

Abstract: 

To reduce the secondary metabolite background in Aspergillus nidulans and minimize the rediscovery of compounds and pathway intermediates, we created a "genetic dereplication" strain in which we deleted eight of the most highly expressed secondary metabolite gene clusters (more than 244,000 base pairs deleted in total). This strain allowed us to discover a novel compound that we designate aspercryptin and to propose a biosynthetic pathway for the compound. Interestingly, aspercryptin is formed from compounds produced by two separate gene clusters, one of which makes the well-known product cichorine. This raises the exciting possibility that fungi use differential regulation of expression of secondary metabolite gene clusters to increase the diversity of metabolites they produce.