James Birrell - Energy Converting Enzymes

Dr. James Birrell
Head of Group Energy Converting Enzymes
Department Inorganic Spectroscopy


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


Selected Publications

  • Sulfide Protects [FeFe] Hydrogenases From O2. Rodríguez-Maciá, P.; Reijerse, E. J.; van Gastel, M.; DeBeer, S.; Lubitz, W.; Rüdiger, O.; Birrell J. A. J. Am. Chem. Soc. 2018 140 9346
  • Unique spectroscopic properties of the H-cluster in a putative sensory [FeFe] hydrogenase. Chongdar, N.; Birrell, J. A.; Pawlak, K.; Sommer, C.; Reijerse, E. J.; Rüdiger, O.; Lubitz, W.; Ogata, H. J. Am. Chem. Soc. 2018 140 1057
  • Reaction coordinate leading to H2 production in [FeFe]-hydrogenase identified by nuclear resonance vibrational spectroscopy and density functional theory. Pelmenschikov, P.; Birrell, J. A.; Pham, C. C.; Wang, H.; Adamska-Venkatesh, A.; Reijerse, E.; Richers, C. P.; Tamasaku, K.; Yoda, Y.; Rauchfuss, T. B.; Lubitz, W.; Cramer, S. P. J. Am. Chem. Soc. 2017 139 16894
  • Intercluster redox coupling influences protonation at the H-cluster in [FeFe] hydrogenases. Rodríguez-Maciá, P.; Pawlak, K.; Rüdiger, O.; Reijerse, E. J.; Lubitz, W; Birrell, J. A. J. Am. Chem. Soc. 2017 139 15122
  • Semisynthetic hydrogenases propel biological energy research into a new era. Birrell, J. A.; Rüdiger, O.; Reijerse, E. J.; Lubitz, W. Joule 2017 1 61
  • Artificial maturation of the highly active heterodimeric [FeFe] hydrogenase from Desulfovibrio desulfuricans ATCC 7757. Birrell, J. A.; Wrede, K.; Pawlak, K.; Rodriguez-Macía, P.; Rüdiger, O.; Reijerse, E. J.; Lubitz, W Isr. J. Chem. 2016 56 852
  • Importance of hydrogen bonding in fine tuning the [2Fe-2S] cluster redox potential of HydC from Thermotoga maritima. Birrell, J. A.; Laurich, C.; Reijerse, E. J.; Ogata, H.; Lubitz W. Biochemistry 2016 55 4344

Full Publicationslist

Group Members

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.