Implementation of communication-mediating domains for non-ribosomal peptide production in Saccharomyces cerevisiae

Saccharomyces cerevisiae has in several cases been proven to be a suitable host for the production of natural products and was recently exploited for the production of non-ribosomal peptides. Synthesis of non-ribosomal peptides (NRPs) is mediated by NRP synthetases (NRPSs), modular enzymes, which are often organized in enzyme complexes. In these complexes, partner NRPSs interact via communication-mediating domains (COM domains). In order to test whether functional interaction between separate NRPS modules is possible in yeast we constructed a yeast strain expressing two modules with compatible COM domains from two plasmids. Successful production as well as secretion of the expected dipeptide was detected. This opens the possibility of using yeast as a eukaryotic platform for fast assessment of new module combinations for the development of novel NRP compounds.