The aim of the project is to translate the knowledge from biosynthetic pathways of natural products into Organic Chemistry, achieved by developing novel chemoenzymatic total syntheses of the polyketide natural products ambruticin and jerangolid. In both biosynthetic pathways, large parts of the molecular complexity are set up by tailoring enzymes. These enzymes will be studied regarding their potential to act as biocatalysts that can substitute late and crucial steps in total syntheses.
The project divides into two parts. At first, the biosynthesis of ambruticin and jerangolid will be studied with a focus on allocating particular steps to individual tailoring enzymes. These enzymes will be characterised in in vitro assays and these assays will be optimised in order to find out if the candidate enzymes can be applied as efficient biocatalysts. After this, total syntheses will be developed, which integrate these enzymatic steps. This approach promises to gain several advantages. The overall efficiency of the syntheses could be drastically improved and the access to derivatives could also be considerably facilitated. Furthermore, the project will gain substantial knowledge about tailoring processes of complex polyketide pathways.
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