Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced Genome Editing
| Autor: | Jakob Weber, Rebecca A. Slotkowski, Axel A. Brakhage, Derek J. Mattern, Uffe Hasbro Mortensen, Vito Valiante, Christina Spuur Nødvig |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genes Fungal Biomedical Engineering Human pathogen Locus (genetics) Biology Biochemistry Genetics and Molecular Biology (miscellaneous) 03 medical and health sciences Genome editing Polyketide synthase Gene cluster Humans CRISPR Selectable marker Gene Editing Genetics Biological Products Cas9 Aspergillus fumigatus General Medicine Mycotoxins 030104 developmental biology Multigene Family biology.protein Synthetic Biology CRISPR-Cas Systems Polyketide Synthases |
| Zdroj: | ACS Synthetic Biology. 6:62-68 |
| ISSN: | 2161-5063 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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