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Year of the Periodic Table - Alexis Hennessy

  • Year: 3rd year PhD
  • Supervisor: Prof. Dominic Campopiano

Protein crystalsTell us about your PhD project

My goal is to use biology to solve the problem of the high economic and environmental costs of fine chemical production. As such, I am engineering enzymes – biological machine which make very complex molecules in living organisms – to make industrially-relevant compounds as a cheaper and greener alternative to current processes.

More specifically, I am interested in engineering a family of enzymes called PreQ0 synthetase to catalyse the coupling between a carboxylic acid and an amine to form an amide. This is one of the most important reactions in drug production yet this still requires polluting organic solvents and non-recyclable coupling agents. This is not cheap and this is not green. As such, I am working on the development of a biocatalytic system which will be able to complete this reaction without the need of any expensive and wasteful coupling agents and which will use water as a green solvent.

Which element is key to your research area and why?

For my research, I get to look a lot at how living organisms produce the complex chemicals they require for their survival. Hence, carbon is definitely key to my research area as this element is the basis of all known life. This is because carbon can create very stable bonds with up to four other atoms so carbon is surely “what holds everything together” in all living organisms, from bacteria and fungi, to us humans.

As such, all biomacromolecules such as DNA, RNA or proteins will have a carbon backbone and all the chemical produced by living organisms will contain mostly carbon. However this definitely doesn’t mean that it is the only important element in life! Hydrogen, nitrogen and oxygen are equally important and many more elements are required in life.

Describe your average day of PhD work here in the School of Chemistry

As many PhD students would probably say, there is no such thing as an average day of PhD work! As my PhD really lies in the interface between Chemistry and Biology, there will be some days where I will have fun cloning and expressing genes to generate the biocatalysts of interest, purifying proteins, designing assays to determine the efficiency of my biocatalyst… – while a fair share of my days would also be spent in the chemistry lab synthesizing the substrates needed for my projects and optimising the reaction conditions for the biotransformations I am interested in.

Experimental apparatus in a fume hood

What’s your favourite chemical element?

My favorite element must be Oganesson because it’s big, complex, probably but not full-on noble and surely very hard to get.

What's your favourite chemical reaction?

Considering my love for medicinal chemistry and my boring unoriginality, I love a good coupling reaction. Sadly, in the like of most things happening in a MedChem lab, it won’t (or shouldn’t) explode, glow in the dark or have funny colours so YouTube videos of coupling reactions would be pretty boring but this is an amazing class of reactions to make very complex molecules as they allow to combine simpler building blocks like Legos. Most of them require expansive transition metal catalysts, however some of them can be catalysed by simpler molecules. For example, the Morita-Baylis-Hillman coupling is a reaction between an aldehyde and an electron-withdrawing alkene which is catalysed by simple organic compounds. Or perhaps, even, protein.