James Birrell - Energy Converting Enzymes


B.Sc./M.Sc.University of Cambridge, UK (2008) 
Ph.D.University of Cambridge, UK (2012) 
PostdocMPI CEC (2013 - 2017) 
Group leaderMPI CEC (since 2018) 


Full publications list | ORCID

Selected MPI CEC publications

  • Chatterjee, S., Harden, I., Bistoni, G., Castillo, R. G., Chabbra, S., van Gastel, M., Schnegg, A., Bill, E., Birrell, J. A., Morandi, B., Neese, F., DeBeer, S. (2022). A Combined Spectroscopic and Computational Study on the Mechanism of Iron-Catalyzed Aminofunctionalization of Olefins Using Hydroxylamine Derived N-O Reagent as the "Amino" Source and "Oxidant". Journal of the American Chemical Society,144(6), 2637-2656. doi:10.1021/jacs.1c11083.
  • Lorenzi, M., Ceccaldi, P., Rodriguez-Macia, P., Redman, H. J., Zamader, A., Birrell, J. A., Meszaros, L. S.,  Berggren, G. (2022). Stability of the H-cluster under whole-cell conditions-formation of an H-trans-like state and its reactivity towards oxygen. Journal of Biological Inorganic Chemistry,27(3), 345-355. doi:10.1007/s00775-022-01928-5.
  • Martini, M. A., Rüdiger, O., Breuer, N., Nöring, B., DeBeer, S., Rodriguez-Macia, P., Birrell, J.  (2021). The Nonphysiological Reductant Sodium Dithionite and [FeFe] Hydrogenase: Influence on the Enzyme Mechanism. Journal of the American Chemical Society, (xx), xx-xx. doi:10.1021/jacs.1c07322.
  • Pelmenschikov, V., Birrell, J. A., Gee, L. B., Richers, C. P., Reijerse, E. J., Wang, H., Arragain, S.; Mishra, N.; Yoda, Y.; Matsuura, H .;Li, L.; Tamasaku, K.; Rauchfuss, T. B.;Lubitz, W., Cramer, S. P. (2021). Vibrational Perturbation of the [FeFe] Hydrogenase H-Cluster Revealed by (CH)-C-13-H-2-ADT Labeling. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,143(22), 8237-8243. doi:10.1021/jacs.1c02323.
  • Hardt, S., Stapf, S., Filmon, D. T., Birrell, J. A., Rüdiger, O., Fourmond, V.,  Léger, C.; Plumeré, N. (2021) Reversible H-2 oxidation and evolution by hydrogenase embedded in a redox polymer film. Nature Catalysis,4(3), 251-258. doi:10.1038/s41929-021-00586-1.
  • Jagilinki, B.P., Ilic, S., Trncik, C., Tyryshkin, A.M., Pike, D.H., Lubitz, W., Bill, E., Einsle, O., Birrell, J.A., Akabayov, B., Noy, D., Nanda, V. (2020). In Vivo Biogenesis of a De Novo Designed Iron−Sulfur Protein ACS Synthetic Biology 9(12), 3400-3407. https://doi.org/10.1021/acssynbio.0c00514
  • Rodríguez-Maciá, P., Breuer, N., DeBeer, S., Birrell, J.A. (2020). Insight into the Redox Behavior of the [4Fe–4S] Subcluster in [FeFe] Hydrogenases ACS Catalysis 10(21), 13084-13095. https://doi.org/10.1021/acscatal.0c02771
  • Sanchez, M.L.K., Konecny, S.E., Narehood, S.M., Reijerse, E.J., Lubitz, W., Birrell, J.A., Dyer, R.B. (2020). The Laser-Induced Potential-Jump: a Method for Rapid Electron Injection into Oxidoreductase Enzymes The Journal of Physical Chemistry B 120(40), 8750-8760.https://doi.org/10.1021/acs.jpcb.0c05718
  • Takeda, K., Kusuoka, R., Birrell, J.A., Yoshida, M., Igarashi, K., Nakamura, N. (2020). Bioelectrocatalysis based on direct electron transfer of fungal pyrroloquinoline quinone-dependent dehydrogenase lacking the cytochrome domain Electrochimica Acta 359, 136982. https://doi.org/10.1016/j.electacta.2020.136982
  • Oughli, A.A., Hardt, S., Rüdiger, O., Birrell, J.A., Plumeré, N. (2020). Reactivation of sulfide-protected [FeFe] hydrogenase in a redox-active hydrogel Chemical Communications 56(69), 9958-9961. https://doi.org/10.1039/D0CC03155K
  • Rodríguez-Maciá, P., Galle, L., Bjornsson, R., Lorent, C., Zebger, I., Yoda, Y., Cramer, S., DeBeer, S., Span, I., Birrell, J.A. (2020). Caught in the Hinact: Crystal Structure and Spectroscopy Reveal a Sulfur Bound to the Active Site of an O2‐stable State of [FeFe] Hydrogenase Angewandte Chemie International Edition 59(38), 16786-16794. https://doi.org/10.1002/anie.202005208
  • Szczesny, J., Birrell, J.A., Conzuelo, F., Lubitz, W., Ruff, A., Schuhmann, W. (2020). Redox polymer‐based high current density gas diffusion H2 oxidation bioanode using [FeFe] hydrogenase from Desulfovibrio desulfuricans in a membrane‐free biofuel cell Angewandte Chemie International Edition 59(38), 16506-16510. https://doi.org/10.1002/anie.202006824
  • Reijerse, E., Birrell, J.A., Lubitz, W. (2020). Spin Polarization Reveals the Coordination Geometry of the [FeFe] Hydrogenase Active Site in Its CO Inhibited State The Journal of Physical Chemistry Letters 11(12), 4597-4602. https://doi.org/10.1021/acs.jpclett.0c01352
  • Van Stappen, C., Decamps, L., Cutsail III, G.E., Bjornsson, R., Henthorn, J.T., Birrell, J.A., DeBeer, S. (2020). The Spectroscopy of Nitrogenases Chemical Reviews 120(12), 5005-5081. https://doi.org/10.1021/acs.chemrev.9b00650
  • Birrell, J.A., Pelmenschikov, V., Mishra, N., Wang, H., Yoda, Y., Tamasaku, K., Rauchfuss, T.B., Cramer, S.P., Lubitz, W., DeBeer, S. (2020). Spectroscopic and Computational Evidence that [FeFe] Hydrogenases Operate Exclusively with CO-bridged Intermediates Journal of the American Chemical Society 142(1), 222-232. https://doi.org/10.1021/jacs.9b09745
  • Chongdar, N., Pawlak, K., Rüdiger, O., Reijerse, E.J., Rodríguez-Maciá, P., Lubitz, W., Birrell, J.A., Ogata, H. (2020). Spectroscopic and biochemical insight into an electron-bifurcating [FeFe] hydrogenase Journal of Biological Inorganic Chemistry 25(1), 135-148. https://doi.org/10.1007/s00775-019-01747-1
  • Reijerse, E.J., Pelmenschikov, V., Birrell, J.A., Richers, C.P., Rauchfuss, T.B., Cramer, S.P., Lubitz, W. (2019). Asymmetry in the Ligand Coordination Sphere of the [FeFe] Hydrogenase Active Site is reflected in the Magnetic Spin Interactions of the Aza-Propanedithiolate Ligand The Journal of Physical Chemistry Letters 10(21), 6794-6799. https://doi.org/10.1021/acs.jpclett.9b02354
  • Sanchez, M.L., Sommer, C., Reijerse, E., Birrell, J.A., Lubitz, W., Dyer, R.B. (2019).  Investigating the Kinetic Competency of CrHydA1 [FeFe] Hydrogenase Intermediate States via Time-resolved Infrared Spectroscopy Journal of the American Chemical Society 141(40), 16064 16070. https://doi.org/10.1021/jacs.9b08348
  • Schuller, J.M., Birrell, J.A., Tanaka, H., Konuma, T., Wulfhorst, H., Cox, N., Schuller, S.K., Thiemann, J., Lubitz, W., Sétif, P., Ikegami, T., Engel, B.D., Kurisu, G., Nowaczyk, M.M. (2019). Structural adaptations of photosynthetic complex I enable ferredoxin-dependent electron transfer Science 363(6424), 257-260. https://doi.org/10.1126/science.aau3613
  • Rodríguez-Maciá, P., Kertess, L., Burnik, J., Birrell, J.A., Hofmann, E., Lubitz, W., Happe, T., Rüdiger, O. (2019). His-ligation to the [4Fe-4S] sub-cluster tunes the catalytic of [FeFe] hydrogenase Journal of the American Chemical Society 141(1), 472-481. https://doi.org/10.1021/jacs.8b11149 
  • Rodriguez-Maciá, P., Reijerse, E.J., van Gastel, M., DeBeer, S., Lubitz, W., Rüdiger, O., Birrell, J.A. (2018). Sulfide Protects [FeFe] Hydrogenases from O2Journal of the American Chemical Society 140(30), 9346-9350. https://doi.org/10.1021/jacs.8b04339 
  • Oughli, A.A., Vélez, M., Birrell, J.A., Schuhmann, W., Lubitz, W., Plumeré, N., Rüdiger, O. (2018). Viologen-modified Electrodes for Protection of Hydrogenases from High Potential Inactivation while Performing H2 Oxidation at Low Overpotential Dalton Transactions 47(31), 10685-10691. https://doi.org/10.1039/C8DT00955D
  • Chongdar, N., Birrell, J.A., Pawlak, K., Sommer, C., Reijerse, E.J., Rudiger, O., Lubitz, W., Ogata, H. (2018). Unique Spectroscopic Properties of the H-Cluster in a Putative Sensory [FeFe] Hydrogenase Journal of the American Chemical Society 140(3), 1057-1068. https://doi.org/10.1021/jacs.7b11287
  • Pelmenschikov, V., Birrell, J.A., Pham, C.C., Mishra, N., Wang, H., Sommer, C., Reijerse, E., Richers, C.P., Tamasaku, K., Yoda, Y., Rauchfuss, T.B., Lubitz, W., Cramer, S.P. (2017). Reaction Coordinate Leading to H2 Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory Journal of the American Chemical Society 139(46), 16894-16902. https://doi.org/10.1021/jacs.7b09751 
  • Rodríguez-Maciá, P., Pawlak, K., Rüdiger, O., Reijerse, E.J., Lubitz, W., Birrell, J.A. (2017). Intercluster Redox Coupling Influences Protonation at the H-cluster in [FeFe] Hydrogenases Journal of the American Chemical Society 139(42), 15122-15134. https://doi.org/10.1021/jacs.7b08193
  • Birrell, J.A., Rüdiger, O., Reijerse, E.J., Lubitz, W. (2017). Semisynthetic Hydrogenases Propel Biological Energy Research into a New Era Joule 1(1), 61-76. doi.org/10.1016/j.joule.2017.07.009
  • Rodríguez-Maciá, P., Reijerse, E., Lubitz, W., Birrell, J.A., Rüdiger, O. (2017). Spectroscopic Evidence of Reversible Disassembly of the [FeFe] Hydrogenase Active Site Journal of Physical Chemistry Letters 8(16), 3834-3839. https://doi.org/10.1021/acs.jpclett.7b01608
  • Rodríguez-Maciá, P., Birrell, J.A., Lubitz, W., Rüdiger, O. (2017). Electrochemical Investigations on the Inactivation of the [FeFe] Hydrogenase from Desulfovibrio desulfuricans by O2 or Light under Hydrogen-Producing Conditions ChemPlusChem 82(4), 540-545. https://doi.org/10.1002/cplu.201600508
  • Sommer, C., Adamska-Venkatesh, A., Pawlak, K., Birrell, J.A., Rüdiger, O., Reijerse, E.J., Lubitz, W. (2017). Proton Coupled Electronic Rearrangement within the H-Cluster as an Essential Step in the Catalytic Cycle of [FeFe] Hydrogenases Journal of the American Chemical Society 139(4), 1440-1443. https://doi.org/10.1021/jacs.6b12636
  • Birrell, J.A., Wrede, K., Pawlak, K., Rodríguez-Maciá, P., Rüdiger, O., Reijerse, E.J., Lubitz, W. (2016). Artificial Maturation of the Highly Active Heterodimeric [FeFe] Hydrogenase from Desulfovibrio desulfuricans ATCC 7757 Israel Journal of Chemistry 56(9-10), 852-863. https://doi.org/10.1002/ijch.201600035
  • Birrell, J.A., Laurich, C., Reijerse, E.J., Ogata, H., Lubitz, W. (2016). Importance of Hydrogen Bonding in Fine Tuning the [2Fe-2S] Cluster Redox Potential of HydC from Thermotoga maritimaBiochemistry 55(31), 4344-4355. https://doi.org/10.1021/acs.biochem.6b00341
  • Kutin, Y., Srinivas, V., Fritz, M., Kositzki, R., Shafaat, H.S., Birrell, J., Bill, E., Haumann, M., Lubitz, W., Högbom, M., Griese, J.J., Cox, N. (2016). Divergent assembly mechanisms of the manganese/iron cofactors in R2lox and R2c proteins Journal of Inorganic Biochemistry 162, 164-177. https://doi.org/10.1016/j.jinorgbio.2016.04.019

Group members


Dr. Maria Alessandra Martini

Lab staff

Nina Breuer
Michael Reus
Adrian van Wasen

Energy Converting Enzymes

Mechanisms of catalysis in energy converting metalloenzymes

Metalloenzymes such as hydrogenases (H2ase), nitrogenase (N2ase), CO dehydrogenase (CODH) and methane monooxygenase (MMO) carry out some of the most fundamental energy converting reactions in nature at very high rates and with very high efficiency using earth abundant metals in their active sites. Despite the importance of these reactions in energy conversion, the mechanisms by which these enzymes carry out their reactions are poorly understood. Using a combination of biochemical, electrochemical and spectroscopic techniques our group is trying to learn how the active site structure and surrounding coordination spheres guide the mechanism of small molecule transformations in these enzymes. In particular, multiple spectroscopic techniques (UV-Vis, IR, Raman, EPR, MCD, Mößbauer and X-ray) are combined to provide a complete picture of the active site and interactions with the surrounding ligands.

Recombinant production of complex metalloproteins

A severe hurdle in studying many metalloproteins is often the low yield and lengthy procedure associated with purification from native host organisms. The enhanced yields, coupled with the simplicity of genetic manipulation, makes over-expression in recombinant hosts such as E. coli an attractive alternative. However, many metalloproteins cannot be easily produced in traditional E. coli systems and so the methods of expression or the hosts used must be further developed. Our group is developing stable recombinant expression systems for high yield production of metalloproteins, particularly sMMO, to facilitate sample intensive spectroscopic investigations such as X-ray absorption spectroscopy.

How proteins tune redox potentials

A key parameter for metalloproteins carrying out redox reactions is the redox potentials of their active site cofactors and the components of their electron transfer chains. How exactly the protein environment influences the cofactor redox potential, including the effects of direct metal ligands as well as more indirect influences such as hydrogen bonding, is a topic of intensive research. Our group is trying to understand these direct and indirect effects using simple iron-sulfur proteins (ferredoxins) as models. These proteins are easy to produce recombinantly in high yields and are easy to crystallize and study their structures. Furthermore, their redox potentials can be easily measured by protein film electrochemistry and their electronic structure probed by a range of spectroscopic methods.