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

Weber J, Valiante V, Nødvig CS, Mattern DJ, Slotkowski RA, Mortensen UH, Brakhage AA (2017) Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced Genome Editing. ACS Synth Biol 6(1), 62-68. PubMed

Abstract

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.

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doi: 10.1021/acssynbio.6b00203 PMID: 27611015