Eukaryotic polyketides in surrogate hosts (EU Project EUKETIDES)
Eukaryotic organisms contain genes encoding the biosynthesis of complex compounds often with useful biological properties. A range of polyketide synthase genes will be isolated and used for production of new biologically active molecules by expression in well characterised bacteria and yeast. These new biosynthetic genes will be combined with known modifying genes for the directed biosynthesis of small libraries of new compounds, resulting in new technology to produce new drugs. Overall we will exploit new advances in genetic, chemistry and fermentation technology to capitalise on leading EU science for the production of high-value new compounds.
Polyketide synthase genes encode for polyketides (polyether compounds), that are a class of naturally occurring molecules produced by bacteria, fungi algae, lichen, and higher plants. These compounds are widely distributed in nature and varied in structure. Importantly, they often posses useful biological activity and many are used as pharmaceuticals or agrochemicals (antibacterial, antiviral, antifungal, anticholesterol, etc.). Algae are known to produce a number of complex biologically active polyketides which can affect other organisms as toxins. These toxins, such as brevetoxin, spirolides, yessotoxin, ciguatoxin, okadaic acid and prymnesin can provoke the neurotoxic shellfish poisining (NSP), the cigutera fish poisoning (CFP), the Diarrhetic shellfish poisoning (DSP) or act as a lytic ichytoxin., but to date no algal PKS genes have been characterised.
Our group has several dozen toxic algae in culture and will produce of some of them cDNA libraries which will be screened with probes for PKS genes. Additionally over hundreds genomic DNAs out of algae DNA-collection will be screened with PKS specific primers for characterisation of novel PKS genes in algae. The resulting PKS genes of the EUKETIDES project will be analysed for their phylogenetic relationships which might help to understand the evolution of a complex multi enzyme complex in such different organism.