Biosynthesis of squalestatins in fungi
Squalestatins are a group of bioactive polyketides that are isolated from various fungi. They consist of an 4,8-dioxabicyclo[3.2.1]octane core and vary in their 1-alkyl and their 6-acyl side chains. As potent Squalene synthase inhibitors various statins are used to lower the plasma cholesterol levels within the treatment of hypercholesterolemia in humans.
The aim of this project is to investigate the biosynthesis of Squalestatin S1 in Phoma sp. C2932 and MF5453, which is carried out by a polyketide synthase. The first challenge of the project will be to identify the gene cluster responsible for the biosynthesis of Squalestatins. Then gene knockout experiments will be performed to establish the role of each gene and hopefully new compounds related to Squalestatin can be produced and their bioactivity tested.