Many diseases, including cancer and antimicrobial-resistant infections, are driven by proteins that are difficult to target using conventional small molecules or biologics. Cyclic peptides offer a powerful solution due to their ability to bind complex protein surfaces with high specificity, yet current methods for discovering and producing these molecules remain slow, costly, and environmentally unsustainable.

Researchers at the University of Bath are developing a bio-based platform to enable the sustainable production and screening of cyclic peptides, unlocking new opportunities for drug discovery against challenging disease targets.

Our approach

This project focuses on engineering a novel intracellular cyclisation system based on enzymatic post-translational modification to generate cyclic peptide libraries directly inside E. coli.

Unlike traditional synthetic approaches, this bio-based system enables the rapid and scalable production of diverse cyclic peptides in living cells. These molecules can be screened in situ for their ability to interact with disease-relevant proteins, providing a powerful route to discover new therapeutics.

By integrating protein engineering, synthetic biology, and high-throughput screening, the project aims to create a sustainable and versatile discovery platform that expands the chemical space accessible for drug development.

Aims and Objectives

The project aims to:

develop an efficient intracellular system for enzymatic peptide cyclisation
generate large and diverse libraries of cyclic peptides in bacterial cells
establish screening platforms to identify peptides that bind challenging drug targets
enable the discovery of novel therapeutic candidates for diseases with unmet clinical need
provide a sustainable and scalable alternative to traditional peptide synthesis
expand access to cyclic peptide chemical space for drug discovery applications

Initial efforts focus on validating the platform using model protein–protein interaction targets relevant to cancer and other complex diseases.

Methods

The research combines synthetic biology, protein engineering, and chemical biology to build and optimise intracellular peptide cyclisation systems. Engineered E. coli strains are used to produce and screen cyclic peptide libraries at scale.

High-throughput screening approaches are integrated with molecular and cellular assays to identify functional peptide binders. Structural and biochemical analyses are used to understand peptide–protein interactions and guide further optimisation.

By coupling library generation and screening within a single biological system, this approach significantly accelerates early-stage discovery while reducing reliance on resource-intensive chemical synthesis.