Open position for a PhD candidate: De novo copper-binding peptides catalyzing radical C-C bond forming reactions (MetRaZymes Doctoral Network)

Keywords. Metalo-peptide, rational design, solid-phase supported peptide synthesis, self-assembly, artificial metalloenzyme.

Context. The “Metal-containing Radical Enzymes” (MetRaZymes) project, a Marie Skłodowska-Curie Doctoral Network (EU), aims at training the future generation of european scientists in the use of metallo-enzymes for the catalysis of radical reactions. The consortia, composed of very diverse expertise (see composition on our website: https://metrazymes.eu), will provide them with a wide overview of state-of-the-art methods and technics. Eventually, this will contribute to enable a sustainable chemical industry in Europe.

Project description. This PhD project aims at developing artificial metalloenzymes ^[1] made of metal-binding de novo peptides, for the catalysis of Atom Transfer Radical reactions. The peptide scaffold will be designed to fold into β-helices. We identified this fold as a very advantageous platform for the development of ArMs provided that (i) there are natural examples of metal-binding β-helices, (ii) they can accommodate loops with high diversity of size and folding, making room for improvement via mutations and (iii) they have the ability to self-assemble into fibers, which can be exploited to build efficient and easy-to-recycle heterogeneous catalysts. Recently in our lab we designed β-helix mimicking peptides that self-assemble into fibers (Lebrun, unpublished data). Building on theses metal-free peptides, the sequence will be mutated so that folded peptide preforms a copper-binding site, without affecting its folding and self-assembling properties. A small library of peptides will be generated, varying the coordinating amino acid residues, the location of the metal site on the helix, and the environment around the metal site.

The Doctoral Candidate (DC) will be involved in the rational design, the synthesis (solid phase peptide synthesis), purification, and structural characterizations (electron microscopy, EPR, CD, UV-Vis, ATR-IR) of these peptides. The catalytic activity of the copper complexes will be evaluated in collaboration with the group of Prof. Nico Bruns (Technical University of Darmstadt, Germany) and with Dr. Sylvain Guizetti from the company NovAliX (Strasbourg, France). Plus, the design will be refined based on modeling in collaboration with the group of Prof. Ivano Eberini (Università degli Studi di Milano, Italy), aiming at generating new generations of metallo-peptides with higher catalytic activity and stereoselectivity. For all these collaborations, the DC will stay onsite, hence learning new technics and gaining an experience in industry.

Profile. The candidate must have a master degree, or equivalent, with a major in Chemistry. Knowledge and experience in chemistry at the interface with biology (eg protein/peptide synthesis, artificial enzymes, enzymatic catalysis, chemical biology) would be a plus. Given that it will be at the frontiers with several disciplines, a high motivation and ability to learn new fundamental knowledge and technics is important.

English (written and spoken) is mandatory for candidate (speaking French is not mandatory). Importantly, applicant must fulfil the eligibility criteria of the MSC Actions, including not having lived in France for more than 12 months between march 2020 and march 2023.

Duration. 36 months, expected to start from 2023 march the 1st.

Working conditions. This PhD position is funded by the EU, as part of the “Metal-Containing Radical Enzymes” (MetRaZymes) project, a Marie Skłodowska-Curie Doctoral Network. The DC will be supervised by Vincent Lebrun (research associate, CNRS) in the group of Prof. Peter Faller (UMR 7177). To know more about our group, please visit our website https://bcb.chimie.unistra.fr. Monthly gross salary will be 3200 euros (salary + mobility allowance). Weekly working time is 37h30, with 42 vacation days a year. Numerous trainings will complete skills portfolio of the Doctoral Candidate (DC). Host institution: University of Strasbourg is one of the largest universities in France, with nearly 51 000 students (including 20 % of international students), internationally recognized in chemistry (with 2 Nobel laureates).

Application process. Applications must be sent to Dr. Vincent Lebrun (vlebrun@unistra.fr) AND to Dr. Raheleh Pardehkhorram (raheleh.pardehkhorram@smartmem.tu-darmstadt.de), before November the 30th 2022. Documents required (compiled as a single PDF): CV (including publication list if any, and two professional references), letter of motivation for this project, copies of degree certificates. After a first selection of candidates, interviews will be conducted via visio-conference.

[1] F. Schwizer, Y. Okamoto, T. Heinisch, Y. Gu, M. M. Pellizzoni, V. Lebrun, R. Reuter, V. Köhler, J. C. Lewis, T. R. Ward, Chem. Rev. 2018, 118, 142–231.