Metalloprotein mimics - old tools in a new light.

Metalloproteins utilize metal cofactors to catalyze essential reactions in all organisms. They carry out thermodynamically challenging substrate conversions such as the oxidation of water or hydrocarbons, the reduction of nitrogen to ammonium, and generation of molecular hydrogen. Besides their fundamental role in nature, metalloenzymes have promising biotechnological applications that aim to generate high-value chemicals, drugs, nutrients, biofuels, or electricity. Recent reports that a chemically synthesized compound is able to reconstitute [2Fe]-hydrogenases, harboring an especially elaborate and highly efficient metal cofactor, promise to pave the way for gaining much deeper insight into the function of even complex metal enzymes. What is more, synthetic biology approaches such as the chemical synthesis of artificial hydrogenases seem to be in reach.

[1]  W. Myers,et al.  Nuclear resonance vibrational spectroscopy and electron paramagnetic resonance spectroscopy of 57Fe-enriched [FeFe] hydrogenase indicate stepwise assembly of the H-cluster. , 2013, Biochemistry.

[2]  L. Curatti,et al.  In vitro synthesis of the iron–molybdenum cofactor of nitrogenase from iron, sulfur, molybdenum, and homocitrate using purified proteins , 2007, Proceedings of the National Academy of Sciences.

[3]  J. W. Peters,et al.  Insights into [FeFe]-hydrogenase structure, mechanism, and maturation. , 2011, Structure.

[4]  L. Ji,et al.  Insights into metalloenzyme microenvironments: biomimetic metal complexes with a functional second coordination sphere. , 2013, Chemical Society reviews.

[5]  P. Siegbahn.  Structures and energetics for O2 formation in photosystem II. , 2009, Accounts of chemical research.

[6]  Sutapa Bose,et al.  A Broader View: Microbial Enzymes and Their Relevance in Industries, Medicine, and Beyond , 2013, BioMed research international.

[7]  Benveniste,et al.  Cytochrome P450 , 1993, Handbook of Experimental Pharmacology.

[8]  J. W. Peters,et al.  Emerging paradigms for complex iron-sulfur cofactor assembly and insertion. , 2012, Annual review of biochemistry.

[9]  K. Hodgson,et al.  Spectroscopic characterization of the isolated iron-molybdenum cofactor (FeMoco) precursor from the protein NifEN. , 2011, Angewandte Chemie.

[10]  Yilin Hu,et al.  Decoding the nitrogenase mechanism: the homologue approach. , 2010, Accounts of chemical research.

[11]  J. W. Peters,et al.  Stepwise [FeFe]-hydrogenase H-cluster assembly revealed in the structure of HydAΔEFG , 2010, Nature.

[12]  P. Vignais,et al.  Occurrence, classification, and biological function of hydrogenases: an overview. , 2007, Chemical reviews.

[13]  W. Lubitz,et al.  Spontaneous activation of [FeFe]-hydrogenases by an inorganic [2Fe] active site mimic. , 2013, Nature chemical biology.

[14]  R. H. Holm,et al.  Biomimetic chemistry of iron, nickel, molybdenum, and tungsten in sulfur-ligated protein sites. , 2009, Biochemistry.

[15]  T. Happe,et al.  Molecular basis of [FeFe]-hydrogenase function: an insight into the complex interplay between protein and catalytic cofactor. , 2013, Biochimica et biophysica acta.

[16]  M. Posewitz,et al.  Crystal Structure of HydF Scaffold Protein Provides Insights into [FeFe]-Hydrogenase Maturation* , 2011, The Journal of Biological Chemistry.

[17]  Keisuke Kawakami,et al.  Crystal structure of oxygen-evolving photosystem II at a resolution of 1.9 Å , 2011, Nature.

[18]  J. W. Peters,et al.  Substrate specificity and evolutionary implications of a NifDK enzyme carrying NifB‐co at its active site , 2010, FEBS letters.

[19]  Vlada B Urlacher,et al.  Cytochrome P450 monooxygenases: an update on perspectives for synthetic application. , 2012, Trends in biotechnology.

[20]  Takashi Hayashi,et al.  A hydrogenase model system based on the sequence of cytochrome c: photochemical hydrogen evolution in aqueous media. , 2011, Chemical communications.

[21]  Xu‐Bing Li,et al.  Chitosan confinement enhances hydrogen photogeneration from a mimic of the diiron subsite of [FeFe]-hydrogenase , 2013, Nature Communications.

[22]  E. Torres,et al.  Apoenzyme reconstitution as a chemical tool for structural enzymology and biotechnology. , 2009, Angewandte Chemie.

[23]  Souvik Roy,et al.  Metalloenzymes: Cutting out the middleman. , 2013, Nature chemical biology.

[24]  D. Rees,et al.  The sixteenth iron in the nitrogenase MoFe protein. , 2013, Angewandte Chemie.

[25]  M. Haumann,et al.  O2 Reactions at the Six-iron Active Site (H-cluster) in [FeFe]-Hydrogenase* , 2011, The Journal of Biological Chemistry.

[26]  P. Holland,et al.  Recent Developments in the Homogeneous Reduction of Dinitrogen by Molybdenum and Iron , 2013 .

[27]  W. Lubitz,et al.  Synthesis and characterization of de novo designed peptides modelling the binding sites of [4Fe-4S] clusters in photosystem I. , 2009, Biochimica et biophysica acta.

[28]  H. Görls,et al.  A Silicon-Heteroaromatic System as Photosensitizer for Light-Driven Hydrogen Production by Hydrogenase Mimics† , 2013 .

[29]  B. Burgess,et al.  Identification of an Fe protein Residue (Glu146) ofAzotobacter vinelandii Nitrogenase That Is Specifically Involved in FeMo Cofactor Insertion* , 2000, The Journal of Biological Chemistry.

[30]  Yi Lu,et al.  Design of functional metalloproteins , 2009, Nature.

[31]  J. Fontecilla-Camps,et al.  Structure-Function Relationships in [FeFe]-Hydrogenase Active Site Maturation* , 2012, The Journal of Biological Chemistry.

[32]  W. Myers,et al.  A Radical Intermediate in Tyrosine Scission to the CO and CN− Ligands of FeFe Hydrogenase , 2013, Science.

[33]  R. Mendel,et al.  Cell biology of molybdenum in plants and humans. , 2012, Biochimica et biophysica acta.

[34]  L. Seefeldt,et al.  Electron transfer in nitrogenase catalysis. , 2012, Current opinion in chemical biology.

[35]  P. Fornasiero,et al.  A Synthetic Nickel Electrocatalyst with a Turnover Frequency above 100 000 s−1 for H2 Production , 2012 .

[36]  W. Lubitz,et al.  Biomimetic assembly and activation of [FeFe]-hydrogenases , 2013, Nature.

[37]  D. Bryant,et al.  Solar hydrogen-producing bionanodevice outperforms natural photosynthesis , 2011, Proceedings of the National Academy of Sciences.

[38]  Michel Frey,et al.  Hydrogenases: Hydrogen‐Activating Enzymes , 2002, Chembiochem : a European journal of chemical biology.

[39]  S. Ragsdale.  Metals and their scaffolds to promote difficult enzymatic reactions. , 2006, Chemical reviews.

[40]  G. Ghirlanda,et al.  De novo design of functional proteins: Toward artificial hydrogenases. , 2013, Biopolymers.

[41]  A. Hemschemeier,et al.  Alternative photosynthetic electron transport pathways during anaerobiosis in the green alga Chlamydomonas reinhardtii. , 2011, Biochimica et biophysica acta.

[42]  R. Mendel,et al.  Molybdenum cofactors, enzymes and pathways , 2009, Nature.

[43]  Michael Hippler,et al.  Characterizing the Anaerobic Response of Chlamydomonas reinhardtii by Quantitative Proteomics , 2010, Molecular & Cellular Proteomics.

[44]  C. Pickett,et al.  Structural and functional analogues of the active sites of the [Fe]-, [NiFe]-, and [FeFe]-hydrogenases. , 2009, Chemical reviews.

[45]  Takashi Hayashi,et al.  Photocatalytic hydrogen evolution by a diiron hydrogenase model based on a peptide fragment of cytochrome c556 with an attached diiron carbonyl cluster and an attached ruthenium photosensitizer. , 2012, Journal of inorganic biochemistry.

[46]  R. Prince,et al.  Characterization of a modified nitrogenase Fe protein from Klebsiella pneumoniae in which the 4Fe4S cluster has been replaced by a 4Fe4Se cluster , 2009, JBIC Journal of Biological Inorganic Chemistry.

[47]  Yuming Xiao,et al.  Extended X-ray absorption fine structure and nuclear resonance vibrational spectroscopy reveal that NifB-co, a FeMo-co precursor, comprises a 6Fe core with an interstitial light atom. , 2008, Journal of the American Chemical Society.