I obtained my MChem in Biological and Medicinal Chemistry from the University of York. My final year project with Paul Walton involved studying two AA10 LPMOs derived from Archaea. This project was my first practical introduction to biochemistry and inspired me to move into chemical biology for my PhD. I was interested in my PhD because of its potential industrial applications, links to green chemistry and how it would develop my skills in in structural biology. I am also passionate about women in STEM and will make this a focus of my outreach work throughout this degree.
Carbon-carbon bond formations are of fundamental importance in synthetic chemistry as they form the scaffold upon which many of the most complex molecules, including pharmaceutical and agricultural chemicals, are based. The use of enzymes to perform these reactions has come into the spotlight in recent years as they offer high activity and selectivity as well as having advantages on the green chemistry front. My project will be focusing on two areas:
Firstly, a 2-oxoglutarate dependent dioxygenase (2-ODD-PH) that catalyses a C-C ring closing reaction of the metabolite yatein to give the product deoxypodophyllotoxin as part of the biosynthesis of the anti-cancer agent etoposide. It has recently been shown that this enzyme can be applied to other closely related substrates, however a structure has yet to be obtained and no protein engineering has been performed that would allow a more detailed interrogation of its mechanism and synthetic potential.
The second part of my project will focus on the enzymes involved in the biosynthetic route of nicotine. Despite the popularity of nicotine, the steps in the late stages of its biosynthesis are yet to be fully characterised. It is thought that the enzymes involved are A622/PIP (homology to isoflavone synthase) and a series of berberine bridge like enzymes. I will be structurally characterising these enzymes and using a variety of methods to investigate their mechanisms and roles.