Genome sequencing and subsequent annotation of several Aspergillus genomes has revealed the presence of a large number of previously unknown putative gene clusters. Many of the clusters contain an interesting class of multi domain enzyme called polyketide synthases (PKS). The synthases are able to catalyze the polymerization of acetyl and propionyl subunits into large molecules that are subsequently modified by neighboring enzymes encoded within each cluster. The result is the formation of complex molecules with a high degree of structural diversity and often a very specific biological activity. These activities have been applied in a range of pharmaceuticals such as antibiotics, cholesterol lowering agents and anti cancer agents. Although, a few polyketide biosynthesis pathways have been elucidated, most clusters still remain to be mapped and characterized. Moreover, very little is known about how individual tailoring enzymes coordinate their activities. In the prese! nt study, we use a combination of reverse genetics and chemical analyses to identify the products of uncharacterized polyketide gene clusters in Aspergillus nidulans. This is specifically done by a combination of promoter replacements and gene deletions. For selected clusters we tag genes with fluorescent proteins to asses the spatial and temporal coordination of the biosynthesis. Examples of this approach are presented.
Full conference title:
6th International Aspergillus Meeting
- Asperfest 6 (2009)