Application of a Synthetic Ferredoxin‐Inspired [4Fe4S]‐Peptide Maquette as the Redox Partner for an [FeFe]‐Hydrogenase

Bombana, Andrea; Shanmugam, Muralidharan; Collison, David; Kibler, Alexander J.; Newton, Graham N.; Jäger, Christof M.; Croft, Anna K.; Morra, Simone; Mitchell, Nicholas J.

Abstract

‘Bacterial-type’ ferredoxins host a cubane [4Fe4S]2+/+ cluster that enables these proteins to mediate electron transfer and facilitate a broad range of biological processes. Peptide maquettes based on the conserved cluster-forming motif have previously been reported and used to model the ferredoxins. Herein we explore the integration of a [4Fe4S]-peptide maquette into a H2-powered electron transport chain. While routinely formed under anaerobic conditions, we illustrate by electron paramagnetic resonance (EPR) analysis that these maquettes can be reconstituted under aerobic conditions by using photoactivated NADH to reduce the cluster at 240 K. Attempts to tune the redox properties of the iron-sulfur cluster by introducing an Fe-coordinating selenocysteine residue were also explored. To demonstrate the integration of these artificial metalloproteins into a semi-synthetic electron transport chain, we utilize a ferredoxin-inspired [4Fe4S]-peptide maquette as the redox partner in the hydrogenase-mediated oxidation of H2.

Citation

Bombana, A., Shanmugam, M., Collison, D., Kibler, A. J., Newton, G. N., Jäger, C. M., …Mitchell, N. J. (2023). Application of a Synthetic Ferredoxin‐Inspired [4Fe4S]‐Peptide Maquette as the Redox Partner for an [FeFe]‐Hydrogenase. ChemBioChem, 24(18), Article e202300250. https://doi.org/10.1002/cbic.202300250

• Journal Article Type: Article
• Acceptance Date: Jun 28, 2023
• Online Publication Date: Jun 30, 2023
• Publication Date: Sep 15, 2023
• Deposit Date: Jul 14, 2023
• Publicly Available Date: Jul 1, 2024
• Journal: ChemBioChem
• Print ISSN: 1439-4227
• Electronic ISSN: 1439-7633
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 18
• Article Number: e202300250
• DOI: https://doi.org/10.1002/cbic.202300250
• Keywords: Iron-sulfur; Peptide; Maquette; hydrogenase; EPR
• Public URL: https://nottingham-repository.worktribe.com/output/22989411
• Publisher URL: https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202300250