Engineering the biosynthesis of non-ribosomal peptides
September 15-19, 2019
Non-ribosomal peptides are a class of natural product that exhibit diverse properties and function as toxins, antibiotics, siderophores, and pigments. Their range of activity means they have roles in medicine, agriculture and bioremediation. Non-ribosomal peptides are biosynthesised by linking monomers together via peptide bonds. They are assembled from a pool of hundreds of monomers, and often contain cyclisation or other modifications not found in ribosomally-synthesised peptides. Their structural diversity means they can be expensive and/or difficult to synthesise. Consequently, many non-ribosomal peptides are produced using fermentation and then modified to generate compounds suitable for medical or industrial applications. Modifying the biosynthetic pathways could provide a cheap and scalable source of new compounds but attempts to engineer them have previously had a low success rate. Using pyoverdine as a model system, this study investigated how to rationally engineer non-ribosomal peptide biosynthesis and generated modified pyoverdines in 6/9 cases. The results of modifying pyoverdine were then used to engineer a second pathway to make dipeptides with a 3/5 success rate. The high success rate and similar results using two biosynthetic pathways suggest this approach is highly transferable and will be valuable for engineering other pathways.
Mark Jonathan Calcott and David Ackerley, "Engineering the biosynthesis of non-ribosomal peptides" in "Enzyme Engineering XXV", Huimin Zhao, University of Illinois at Urbana-Champaign, USA John Wong, Pfizer, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/enzyme_xxv/45