Electrified and Nanoconfined Enzymes: The Electrochemical Leaf

A funded PhD studentship is available in the group of Dr Clare F Megarity at the University of Manchester, for an ambitious candidate interested in a brand-new way to study and exploit enzyme catalysis using a powerful electrochemical platform called The Electrochemical Leaf (e-Leaf).

The e-Leaf resulted from two discoveries made in the last five years: (i) the ability to use electricity to power and control the enzyme central to photosynthesis, ferredoxin NADP⁺ reductase (FNR), whilst entrapped in a highly porous metal oxide electrode and (ii) the entrapment and crowding of additional enzymes and enzyme cascades in the porous electrode where they are driven via coupling to FNR’s catalysis, the rapid and reversible interconversion of NADP⁺/NADPH. 

In photosynthesis, electrons excited by sunlight are transferred directly from an electron-carrier protein, ferredoxin, to the active site flavin in FNR. FNR uses these electrons to catalyse the reduction of NADP⁺ to NADPH, providing reducing equivalents to the biosynthetic enzyme cascade, the Calvin Cycle. In the Electrochemical Leaf, sunlight is replaced by electricity and ferredoxin is replaced by a highly porous indium tin oxide electrode. FNR adsorbs tightly in these pores where, under potential control, fast electron exchange between its active site flavin and the electrode, allows it to catalyse the bidirectional interconversion of NADP⁺/NADPH which can subsequently be used by a dehydrogenase enzyme co-entrapped in the pores. In this crucial step, FNR transduces the electricity to connect to enzymes which are not electrochemically accessible - a gateway to power a myriad of enzyme cascades which require only one enzyme to be NADP(H)-dependent as a connector to FNR. 

All the enzymes are nanoconfined and highly crowded in the electrode pores, an environment that mirrors the true conditions under which enzymes function in nature, providing important advantages: a high local enzyme concentration and the retention of intermediates and exchangeable cofactors so that they are channelled or recycled before diffusing away.

Monitoring enzymes as they function in this crowd gives unrivalled authentic enzymological insight (compared to typical approaches which monitor enzyme activity in dilute solution). This, coupled with the power to use unmediated electrochemistry to control the direction and magnitude of the driving force, and to observe the catalysis in real-time, makes the e-Leaf unique as an enzyme interrogator. 

The power of the e-Leaf has already been exploited for diverse avenues of research^1-5; recent work exploits the crowded nanoconfinement to extend the concept to confocal recycling of both NADP(H) and ATP⁶.    

Research in this group exploits the e-Leaf’s unique power taking it in new research directions: for the study of enzymes and cascades involved in disease and antibiotic resistance, for enzyme discovery and for enzyme engineering for biosynthesis. Additionally, new research focuses on the design of different nanoconfined and crowded enzyme-porous electrodes. The PI has several PhD projects in mind which fall under these themes, to be discussed with the successful candidate.  

This research is interdisciplinary, and will involve training in bioelectrochemistry, enzyme biochemistry, enzyme engineering and electrode fabrication. This is a new group and training will be delivered from the PI, Dr Clare F Megarity.

‪Clare F. Megarity - ‪Google Scholar

Admissions Requirements:

Applicants should have or expect to achieve at least a 2.1 honours degree in Chemistry, Biochemistry or a related discipline.  

To apply for this project, please submit an online application using this link: How to apply for postgraduate research at The University of Manchester

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. We know that diversity strengthens our research community, leading to enhanced research creativity, productivity and quality, and societal and economic impact. We actively encourage applicants from diverse career paths and backgrounds and from all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status.

We also support applications from those returning from a career break or other roles. We consider offering flexible study arrangements (including part-time: 50%, 60% or 80%, depending on the project/funder).