Engineering Fungal Nonribosomal Peptide Synthetases for Novel Alkaloids

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This project aims to use protein-domain shuffling aided by structural biology to decode and engineer a class of modular megaenzymes, called nonribosomal peptide synthetases (NRPSs), in fungi. These are responsible for the biosynthesis of peptide-derived bioactive molecules, such as the antibiotic penicillin and the immunosuppressant cyclosporin. Expected outcomes of this project include a fungal NRPS engineering platform for generating new molecules with desirable biological activities that can be readily scaled up for sustainable bioproduction. This will provide significant benefits to Australia through the development of cutting-edge biotechnologies as well as the discovery of new pharmaceuticals, veterinary products and agrichemicals.