[Expired] PhD thesis offer in bioinorganic chemistry : Deciphering the reaction mechanism of CODH,a key enzyme in CO/CO2 interconversion

Financing: Labex Arcane (https://arcane.univ-grenoble-alpes.fr)
Place of work: CEA/LCBM, Grenoble, France (https://www.cbm-lab.fr/en)
Directors of thesis: Dr. Ragnar Bjornsson (CEA Grenoble), Dr. Christine Cavazza (CEA Grenoble)
PhD starting date: October 2024

Keywords: Bioinorganic chemistry, computational chemistry, crystallography, metallobiochemistry, metalloenzymes, small-molecule activation, catalysis, multiscale modelling, QM/MM, iron-sulfur clusters

This PhD thesis project will be carried out in collaboration between the computational chemistry and X-rays team (CoMX) and the bioenergy and environment team (BEE) at the laboratory for chemistry and biology of metal laboratory (LCBM) at the CEA (https://www.cbm-lab.fr/en).

The purpose of the project is to uncover the mechanism of how Nature reduces CO2 and oxidizes CO by the Ni,Fe-dependent CO dehydrogenase, the most proficient catalyst for  CO/CO2 interconversion.

Context and objectives
Carbon monoxide dehydrogenase (CODH) is a vital enzyme of the carbon cycle, being responsible for CO/CO2 interconversion. The 2-electron reduction of CO2 to CO is furthermore a key step in chemical carbon recycling, the conversion of the green-house gas CO2 towards useful carbon-based products. The enzyme catalyzes this reaction in either direction with very small overpotential and fast rates. However, despite decades of biochemical, crystallographic, and spectroscopic work, the enzyme reaction mechanism is still under debate, hindering bioinspired catalyst design from fully reaching its potential. In particular, the nature of the reduced Cred2 state and how it binds CO2 and cleaves it to CO and H2O is unclear and even controversial. There is a disconnect between an experimental X-ray structure of Cred2 and spectroscopic work with various hypotheses having been suggested to account for the added 2 e-, such as a Ni(0) reduced species, Ni-hydride or a Ni-Fe metal-metal bond.
In this PhD project we will take a fresh new look at this fascinating system through a combined approach of X-ray crystallography, modern multiscale modelling QM/MM techniques and quantum crystallographic refinement. New attempts at acquiring crystal structures of the Cred2 state and others in both native and mutant forms will be carried out, guided by multiscale modelling.

Applicant profile
Candidates should a master‘s degree in chemistry or biochemistry and should have an interest in bioinorganic chemistry, biochemistry, computational chemistry or inorganic chemistry. Experience in either computational chemistry or crystallography is an advantage.

Candidates should have an interest in multidisciplinary work as the project involves both computational and experimental work. A strong command of English is required.

Apply before April 15th, 2024.

For more information and application
Please contact us with a CV and motivation letter:

Deadline: Apply before April 15th, 2024

Web: https://www.cbm-lab.fr/en