Novel Synthetic Biology for the Generation of 'Unnatural' Peptides

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Many bioactive natural products currently utilised as anticancer and antibiotic agents are biosynthesized in microorganisms by multifunctional enzymes known as nonribosomal peptide synthetases (NRPSs). These naturally occurring 'peptide factories' are seen as the promising starting point for the development of novel synthetic biology towards the generation of 'unnatural' peptides: these are molecules still produced via biosynthesis but are structurally different from the original peptide products, and may be of equal or superior value.The aim of this PhD project is to develop a novel chemoenzymatic approach towards the in vivo generation of unnatural peptides: by utilising chemical building blocks and engineered NRPS enzymes/pathways it is hoped to generate a library of novel peptide compounds of pharmaceutical and industrial interest.