Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced Genome Editing.

Filamentous fungi produce varieties of natural products even in a strain dependent manner. However, the genetic basis of chemical speciation between strains is still widely unknown. One example is trypacidin, a natural product of the opportunistic human pathogen Aspergillus fumigatus, which is not produced among different isolates. Combining computational analysis with targeted gene editing, we could link a single nucleotide insertion in the polyketide synthase of the trypacidin biosynthetic pathway and reconstitute its production in a nonproducing strain. Thus, we present a CRISPR/Cas9-based tool for advanced molecular genetic studies in filamentous fungi, exploiting selectable markers separated from the edited locus.

Molecular and Applied Microbiology Biobricks of Microbial Natural Product Syntheses

Prof. Dr. Axel A. Brakhage Dr. Vito Valiante Dr. Derek J. Mattern Dr. Jakob Weber

doi: 0.1021/acssynbio.6b00203 PMID: 27611015