Our work on enzymology is driven by an interest in biochemical pathways and the complex reactions that enable natural product biosynthesis. Many of these reactions (stereo and regio selective inert C-H functionalisation, peptide cyclisation, selective halogenation) have no analogue from standard synthetic methodology. 

In the drive to make synthetic chemistry more sustainable we believe many of these enzymes have potential as biocatalysis and could provide solutions to reducing our reliance on heavy metal catalysis while also providing a range of new chemistries to exploit.

We work in collaboration with Dr. D. Castagnolo (UCL) on developing enzymes from fundamental investigation to application in biocatalysis.

Our work is driven by our fascination with the ability of microbes to produce highly complex specialised metabolites, many of which have important bioactivity.Antimicrobial resistance is a major global health crisis, with resistance a particular problem in Gram negative organisms. In the 20th century most of our antibiotics have been produced successfuly by fermentation of a producing bacteria or fungus. However, developing derivatives of such molecules to avoid resistance is challenging requiring significant pathway engineering.

Our investigations lead us in several directions including:

• Genome mining towards cyclic peptide discovery and isolation.

• Investigation and understanding of cyclic peptide biosynthetic pathways.

• Manipulation of biosynthetic pathways to produce novel derivatives.

• Mechanism of action of natural products including pathogenicity factors.

Cyclic peptides have been vital antimicrobials and now are of increasing interest in drug discovery and development.

• We have developed novel chemistry to enable rapid peptide cyclisation under mild conditions with excellent selectivity. 

• We are interested in developing methods to develop derivatives of natural product cyclic peptides using chemoenzymatic methods to identify new targets to enable focused use of pathway engineering towards a defined target.