Next generation enzymatic assembly of peptide therapeutics (NXPEP)

Peptides are fundamental in life and have been developed as essential medicines, vaccines, biomaterials for tissue engineering, drug delivery and nanotechnology applications. Currently there are more than 80 peptide drugs approved world-wide, with many more in clinical trials, including essential antibiotics, antiviral and anticancer agents as well as treatments for diabetes and many other important diseases. Most peptides are produced in the lab using solid phase peptide synthesis (SPPS) technology and related chemical methods that are outdated, problematic to scale-up, require large amounts of deleterious reagents and solvents that are damaging to the environment. We will solve this long-standing problem by developing the first viable enzymatic approach for more sustainable peptide synthesis, using engineered ligase enzymes to couple amino acids together under mild, benign, aqueous conditions. Our next generation enzymatic peptide assembly (NXPEP) technology will provide cleaner, scalable, and more efficient ways to produce peptides. In addition to providing more affordable peptide therapeutics, which are widely needed in the less affluent and developing regions of the world, NXPEP can open up new horizons across many other scientific fields (e.g. biomaterials). The aims of the PhD project are: (i) Use bioinformatics approaches to discover new ligases from nature, that facilitate peptide assembly and functionalisation; (ii) Develop directed evolution approaches to improve ligase enzymes with increased activity and substrate scope for peptide assembly; (iii) Scale-up NXPEP processes, for producing target peptides using novel separation methods to isolate peptide products.