Synthetic biology approach to obtain novel antimicrobials with cyclic modifications
Extensive use of antibiotic substances in medicine and agriculture has resulted in an increase of antibiotic-resistant bacteria, necessitating the development of novel antimicrobial compounds from alternative sources. The ribosomally synthesized and post-translationally modified peptides (RiPPs) entails diverse natural products and their ribosomal origin enables strategies to modify the peptide sequence and to create variants with altered biological and physico-chemical properties.
To investigate circularin A, a circular bacteriocin produced by Clostridium beijerinckii ATCC 25752 and active against Clostridium perfringens, is expressed heterologously in diverse hosts. The extraordinary leader peptide (only 3 amino acids) makes this modification machinery highly attractive for biosynthetic peptide manipulations. Ultimately we want to combine different RiPP modification machineries to make new-to-nature molecules containing multiple post-translational modifications.
We will use a synthetic biology approach to design and produce innovative modular systems for introducing various circular modifications into peptides. Combination of peptide modification modules will yield different peptides with improved stability and novel bioactivities.
Molecular cloning techniques; Expression and purification of peptides; Antimicrobial activity assays; Mass spectrometry and data analysis