Microbes harbour extraordinary potential to produce complex chemicals encoded within biosynthetic gene clusters (BGCs), yet most remain silent or inactive under laboratory conditions. Our research addresses fundamental questions about pathway regulation and biosynthesis while also developing strategies to unlock silent BGCs. While basic science has a prominent role in our approach, we consider how research can be applied to global challenges including antimicrobial resistance, sustainable crop protection, and replacing petrochemical synthesis with biological alternatives. We specialise in engineering Streptomyces venezuelae, a fast-growing synthetic biology model, to discover and produce novel bioactive compounds.

Our basic research focuses on understanding mechanistic questions such as pathway regulation, single enzyme characterisation all the way through to complex multistep biosynthetic pathways. This fundamental knowledge also enables applied outcomes including enzyme discovery, pathway engineering, and production of high-value chemicals and novel biotherapeutics. We employ synthetic biology tools including CRISPR-Cas9, heterologous expression hosts, and pathway refactoring to both elucidate natural biosynthetic mechanisms and unlock nature's hidden chemical diversity for therapeutic and industrial translation.

We pioneer the development of high-yielding cell-free expression systems for academic and industrial purposes, creating extracts from diverse bacteria and optimising systems to achieve high peptide/protein yields (up to 4 mg/mL). Cell-free systems are part of a growing area of research, with a broad variety of applications (e.g., high-value peptides/proteins, high-throughput screening, biosensors, and flexible engineering of pathways). One of the key advantages of cell-free is its capability with high-throughput screening using liquid handling robotics.

Our cell-free toolkits spans model organisms like E. coli to non-model species including Streptomyces venezuelae and Klebsiella pneumoniae, enabling rapid prototyping of biosynthetic pathways and gene expression regulation, without the constraints of living cells. We have established automated platforms for scalable biosynthesis and developed a dedicated Streptomyces cell-free toolkit for natural product discovery.

As co-organisers of the London Cell-free Biological Products Network, we bring together diverse researchers from academia and industry to discuss cell-free systems at the interface of synthetic biology and biotechnology applications. This network meets twice per year at Imperial and UCL.

Antimicrobial resistance is a global challenge which we address through an innovative platform: cell-free protein synthesis as a rapid tool for studying antimicrobial sensitivity and resistance mechanisms.

Our BBSRC-funded collaboration with the UK Health Security Agency (UKHSA) focuses on developing alternative antimicrobials and understanding resistance evolution in ESKAPE pathogens, such as Klebsiella pneumoniae and Acinetobacter baumannii. Our cell-free platform enables rapid testing of antimicrobial peptides and proteins, including engineered variants, without the constraints of living cells, allowing quick assessment of new compounds and understanding of resistance mechanism evolution.