Team:Potsdam Bioware

Modification, Selection and Production of Cyclic Peptides for Therapy

One key task of biopharmaceuticals is the binding and blocking of deregulated proteins. Towards this goal, we mutate and select microviridins, which are tricyclic depsipeptides from cyanobacteria. They are small but stable due to their post-translational side-chain crosslinking. Microviridins have a high potential for therapy as they can block disease-relevant proteases. Yet, the possibilities of cyclic peptides are largely untapped since genetic systems for optimization are not well established. Thus, we developed synthetic systems for the mutation, selection and production of such peptides. We use the 6.5 kb microviridin (mdn) gene cluster cloned in E. coli plasmids, established random mutagenesis and generated focused libraries of microviridins. For selection against a panel of proteases, we are applying and testing phage display, and we are constructing a novel in-vivo selection device, which links protease blocking to antibiotic resistance. Our systems, including the 6.5 kb cluster, adhere to the BioBrick standards.