Genome wide polyketide synthase gene deletion library in Aspergillus nidulans.

Uffe H. Mortensen, Michael L. Nielsen, Jakob B. Nielsen, Christian Rank, Marie L. Klejnstrup, Dorte K. Holm, Katrine H. Brogaard, Bjarne G. Hansen, Jens C. Frisvad, Thomas O. Larsen

Author address: 

Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark, Sí¸ltofts Plads B221/B223, 2800 Kgs. Lyngby, Denmark

Abstract: 

Filamentous fungi produce a wealth of secondary metabolites that dramatically influence human life as they comprise both mycotoxins and pharmaceuticals. To forward the understanding of fungal secondary metabolism we have adopted a multidisciplinary strategy based on fungal ecology, analytical chemistry and molecular biology. Here we present an analysis of a library containing individual deletions of all known and putative PKS genes in the model fungus Aspergillus nidulans. The library has been challenged on a number of different media to uncover new links between genes and polyketide products. At our conditions, we detect several of the known products of A. nidulans including the PKS gene responsible for production of austinol. The validity of this conclusion is ensured by further mutagenesis including site directed mutagenesis of the locus as well as ectopic expression of the gene to indentify the first intermediate in austinol production. Based on our findings we call the gene ausA. Moreover, our results demonstrate several examples of crosstalk between different pathways in polyketide synthesis. To this end, it is important to stress that by investigating a genome wide deletion library at different conditions the chance of mis-assigning genetic links to products due to such crosstalk is dramatically reduced. Together the results and conclusions presented constitute our first step towards a systems understanding of the secondary metabolism of A. nidulans.
2011

abstract No: 

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Full conference title: 

26th Fungal Genetics Conference
    • Fungal Genetics Conference 26th (2005)