A Synthetic Biology Approach for the Total Biosynthesis of Semi-Synthetic Antibiotics

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Currently, derivatives of natural products, widely-used as antibiotics, agrochemicals and other valuable compounds, are manufactured using multi-step processes. This project will develop a scalable, cleaner and more competitive single-step process for the manufacture of high value natural product derivatives, including antibiotics. Improved approaches to pathway engineering, utilising advances in DNA assembly and gene editing, will enable the total biosynthesis of the target antibiotics, circumventing the need for additional transformations. We will use directed evolution and structure-guided engineering to generate new biosynthetic enzymes with novel activities to create new pathways to the antibiotics. Additionally, the use of biosensors controlling GFP will aid the selection of the best mutant enzymes and pathways producing the highest levels of antibiotics. Strains will be optimised for the production of target antibiotics by deleting unnecessary genes, while ensuring that precursor supply is maintained when new engineered genes are introduced.

As described in proposal submitted to IUK.