Cyanobacterial hydrogenases: diversity, regulation and applications.

Cyanobacteria may possess two distinct nickel-iron (NiFe)-hydrogenases: an uptake enzyme found in N(2)-fixing strains, and a bidirectional one present in both non-N(2)-fixing and N(2)-fixing strains. The uptake hydrogenase (encoded by hupSL) catalyzes the consumption of the H(2) produced during N(2) fixation, while the bidirectional enzyme (hoxEFUYH) probably plays a role in fermentation and/or acts as an electron valve during photosynthesis. hupSL constitute a transcriptional unit, and are essentially transcribed under N(2)-fixing conditions. The bidirectional hydrogenase consists of a hydrogenase and a diaphorase part, and the corresponding five hox genes are not always clustered or cotranscribed. The biosynthesis/maturation of NiFe-hydrogenases is highly complex, requiring several core proteins. In cyanobacteria, the genes that are thought to affect hydrogenases pleiotropically (hyp), as well as the genes presumably encoding the hydrogenase-specific endopeptidases (hupW and hoxW) have been identified and characterized. Furthermore, NtcA and LexA have been implicated in the transcriptional regulation of the uptake and the bidirectional enzyme respectively. Recently, the phylogenetic origin of cyanobacterial and algal hydrogenases was analyzed, and it was proposed that the current distribution in cyanobacteria reflects a differential loss of genes according to their ecological needs or constraints. In addition, the possibilities and challenges of cyanobacterial-based H(2) production are addressed.

[1]  D. Bryant,et al.  Growth on Urea Can Trigger Death and Peroxidation of the Cyanobacterium Synechococcus sp. Strain PCC 7002 , 1998, Applied and Environmental Microbiology.

[2]  H. Bothe,et al.  The reversible hydrogenase inAnacystis nidulans is a component of the cytoplasmic membrane , 1991, Naturwissenschaften.

[3]  M. Ludwig,et al.  Occurrence of Hydrogenases in Cyanobacteria and Anoxygenic Photosynthetic Bacteria: Implications for the Phylogenetic Origin of Cyanobacterial and Algal Hydrogenases , 2006, Journal of Molecular Evolution.

[4]  Peter Lindblad,et al.  A hydrogen-producing, hydrogenase-free mutant strain of Nostoc punctiforme ATCC 29133 , 2002 .

[5]  J. W. Golden.  Programmed DNA Rearrangements in Cyanobacteria , 1998 .

[6]  J. Gallon,et al.  N2 Fixation by non-heterocystous cyanobacteria , 1997 .

[7]  Peter Lindblad,et al.  Gas Exchange in the Filamentous Cyanobacterium Nostoc punctiforme Strain ATCC 29133 and Its Hydrogenase-Deficient Mutant Strain NHM5 , 2004, Applied and Environmental Microbiology.

[8]  G. Codd,et al.  The Uptake and Production of Molecular Hydrogen by Unicellular Cyanobacteria , 1985 .

[9]  J. Meyer,et al.  Classification and phylogeny of hydrogenases. , 2001, FEMS microbiology reviews.

[10]  Olaf Kruse,et al.  Photosynthesis: a blueprint for solar energy capture and biohydrogen production technologies , 2005, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[11]  Takakazu Kaneko,et al.  CyanoBase, a www database containing the complete nucleotide sequence of the genome of Synechocystis sp. strain PCC6803 , 1998, Nucleic Acids Res..

[12]  H. Bothe,et al.  Cloning, molecular analysis and insertional mutagenesis of the bidirectional hydrogenase genes from the cyanobacterium Anacystis nidulans , 1996, FEBS letters.

[13]  W. Vermaas,et al.  Succinate Dehydrogenase and Other Respiratory Pathways in Thylakoid Membranes of Synechocystis sp. Strain PCC 6803: Capacity Comparisons and Physiological Function , 2001, Journal of bacteriology.

[14]  Röbbe Wünschiers,et al.  Presence and expression of hydrogenase specific C-terminal endopeptidases in cyanobacteria , 2003, BMC Microbiology.

[15]  D. Rees,et al.  Structural basis of biological nitrogen fixation , 2005, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[16]  Y. Mao,et al.  Cloning and Characterization of hoxH Genes from Arthrospira and Spirulina and Application in Phylogenetic Study , 2005, Marine Biotechnology.

[17]  D. Borthakur,et al.  The use of a PCR cloning and screening strategy to identify lambda clones containing the hupB gene of Anabaena sp. strain PCC7120 , 1996 .

[18]  R. Schulz,et al.  Sequence analysis of an operon of a NAD(P)-reducing nickel hydrogenase from the cyanobacterium Synechocystis sp. PCC 6803 gives additional evidence for direct coupling of the enzyme to NAD(P)H-dehydrogenase (complex I). , 1996, Biochimica et biophysica acta.

[19]  Peter Lindblad,et al.  Photoproduction of H2 by wildtype Anabaena PCC 7120 and a hydrogen uptake deficient mutant: from laboratory experiments to outdoor culture , 2002 .

[20]  G. Maróti,et al.  The hydrogenases of Thiocapsa roseopersicina. , 2005, Biochemical Society transactions.

[21]  Ilana Berman-Frank,et al.  Nitrogen fixation and photosynthetic oxygen evolution in cyanobacteria. , 2003, Research in microbiology.

[22]  Geoffrey D. Smith,et al.  THE HYDROGEN METABOLISM OF CYANOBACTERIA (BLUE‐GREEN ALGAE) , 1981 .

[23]  J. William Schopf,et al.  The Fossil Record: Tracing the Roots of the Cyanobacterial Lineage , 2000 .

[24]  P. Lindblad,et al.  Reversible hydrogenase in Anabaena variabilis ATCC 29413 , 1994, Archives of Microbiology.

[25]  Y. Hihara,et al.  DNA Microarray Analysis of Cyanobacterial Gene Expression during Acclimation to High Light , 2001, Plant Cell.

[26]  P. Wright,et al.  Comparison of protein and peptide prefractionation methods for the shotgun proteomic analysis of Synechocystis sp. PCC 6803 , 2005, Proteomics.

[27]  A. Böck,et al.  HybF, a Zinc-Containing Protein Involved in NiFe Hydrogenase Maturation , 2004, Journal of bacteriology.

[28]  P. Lindblad,et al.  LexA, a transcription regulator binding in the promoter region of the bidirectional hydrogenase in the cyanobacterium Synechocystis sp. PCC 6803. , 2005, FEMS microbiology letters.

[29]  Satoshi Tabata,et al.  Synechocystis sp. PCC 6803 — a useful tool in the study of the genetics of cyanobacteria , 2004, Photosynthesis Research.

[30]  P. Lindblad,et al.  Cyanobacterial H2 production — a comparative analysis , 2004, Planta.

[31]  A. Böck,et al.  Analysis of the cleavage site specificity of the endopeptidase involved in the maturation of the large subunit of hydrogenase 3 from Escherichia coli , 2000, Archives of Microbiology.

[32]  Michel Frey,et al.  Crystal structure of the nickel–iron hydrogenase from Desulfovibrio gigas , 1995, Nature.

[33]  R. Ueda,et al.  Improvement of microalgal photosynthetic productivity by reducing the content of light harvesting pigment , 1999, Journal of Applied Phycology.

[34]  J. Sjöholm,et al.  Transcription and regulation of the hydrogenase(s) accessory genes, hypFCDEAB, in the cyanobacterium Lyngbya majuscula CCAP 1446/4 , 2007, Archives of Microbiology.

[35]  P. Lindblad,et al.  Heterocyst-Specific Excision of the Anabaena sp. Strain PCC 7120 hupL Element Requires xisC , 2005, Journal of bacteriology.

[36]  J. P. Houchins.  The physiology and biochemistry of hydrogen metabolism in cyanobacteria , 1984 .

[37]  Matthew C. Posewitz,et al.  Functional Studies of [FeFe] Hydrogenase Maturation in an Escherichia coli Biosynthetic System , 2006, Journal of bacteriology.

[38]  Laura M Patterson-Fortin,et al.  A LexA-related protein regulates redox-sensitive expression of the cyanobacterial RNA helicase, crhR , 2006, Nucleic acids research.

[39]  R. Maier,et al.  Characterization of Helicobacter pylori Nickel Metabolism Accessory Proteins Needed for Maturation of both Urease and Hydrogenase , 2003, Journal of bacteriology.

[40]  D. Borthakur,et al.  Organization of the hupDEAB genes within the hydrogenase gene cluster of Anabaena sp. strain PCC7120 , 1998, Journal of Applied Phycology.

[41]  O. Lenz,et al.  Light-driven Hydrogen Production by a Hybrid Complex of a [NiFe]-Hydrogenase and the Cyanobacterial Photosystem I , 2006, Photochemistry and photobiology.

[42]  Jun Sun,et al.  Proteomic study of the peripheral proteins from thylakoid membranes of the cyanobacterium Synechocystis sp. PCC 6803 , 2000, Electrophoresis.

[43]  A. Kumar,et al.  CARBON NUTRITION AND THE REGULATION OF UPTAKE HYDROGENASE ACTIVITY IN FREE-LIVING AND SYMBIOTIC ANABAENA CYCADEAE. , 1986, The New phytologist.

[44]  E. Leitão,et al.  Uptake hydrogenase in cyanobacteria: novel input from non-heterocystous strains. , 2005, Biochemical Society transactions.

[45]  K Schulten,et al.  Approaches to developing biological H(2)-photoproducing organisms and processes. , 2005, Biochemical Society transactions.

[46]  Lucas J. Stal,et al.  Fermentation in cyanobacteria , 1997 .

[47]  E. Greenbaum,et al.  A new oxygen sensitivity and its potential application in photosynthetic H2 production , 2003 .

[48]  F. Mayer,et al.  Localization of the Reversible Hydrogenase in Cyanobacteria , 1989 .

[49]  D. Friedman,et al.  Integration host factor: A protein for all reasons , 1988, Cell.

[50]  A. Böck,et al.  Properties of the [NiFe]‐hydrogenase maturation protein HypD , 2006, FEBS letters.

[51]  P. Lindblad,et al.  Immunological characterization of hydrogenases in the nitrogen-fixing cyanobacterium Nostoc sp. strain PCC 73102 , 1995, Current Microbiology.

[52]  P. Böger,et al.  Physiological factors determining hydrogenase activity in nitrogen-fixing heterocystous cyanobacteria. , 1989, Plant physiology.

[53]  R. Huber,et al.  Crystal structure of the hydrogenase maturating endopeptidase HYBD from Escherichia coli. , 1999, Journal of molecular biology.

[54]  R. Huber,et al.  Nickel serves as a substrate recognition motif for the endopeptidase involved in hydrogenase maturation. , 2000, European journal of biochemistry.

[55]  Y. Asada,et al.  Heterologous expression of clostridial hydrogenase in the Cyanobacterium synechococcus PCC7942. , 2000, Biochimica et biophysica acta.

[56]  Genes involved in the maturation of hydrogenase(s) in the nonheterocystous cyanobacterium Lyngbya majuscula CCAP 1446/4 , 2006 .

[57]  H. Bothe,et al.  The utilization of molecular hydrogen by the blue-green alga Anabaena cylindrica , 1977, Archives of Microbiology.

[58]  S. Bhattacharya,et al.  Hydrogen production by Cyanobacteria , 2005, Microbial Cell Factories.

[59]  P. Lindblad,et al.  Transcriptional regulation of Nostoc uptake hydrogenase. , 1999, FEMS microbiology letters.

[60]  T. Antal,et al.  Production of H2 by sulphur‐deprived cells of the unicellular cyanobacteria Gloeocapsa alpicola and Synechocystis sp. PCC 6803 during dark incubation with methane or at various extracellular pH , 2005, Journal of applied microbiology.

[61]  R. Maier,et al.  Requirement of nickel metabolism proteins HypA and HypB for full activity of both hydrogenase and urease in Helicobacter pylori , 2001, Molecular microbiology.

[62]  Paula Tamagnini,et al.  Hydrogenases and Hydrogen Metabolism of Cyanobacteria , 2002, Microbiology and Molecular Biology Reviews.

[63]  P. Lindblad,et al.  Induction of H2-Uptake and Nitrogenase Activities in the Cyanobacterium Anabaena variabilis ATCC 29413: Effects of Hydrogen and Organic Substrate , 1996, Current Microbiology.

[64]  J. Palacios,et al.  Gene Products of the hupGHIJ Operon Are Involved in Maturation of the Iron-Sulfur Subunit of the [NiFe] Hydrogenase from Rhizobium leguminosarum bv. viciae , 2005, Journal of bacteriology.

[65]  Hong Li,et al.  Differential Gene Expression in Response to Hydrogen Peroxide and the Putative PerR Regulon of Synechocystis sp. Strain PCC 6803 , 2004, Journal of bacteriology.

[66]  M. Asayama,et al.  Nitrogen induction of sugar catabolic gene expression in Synechocystis sp. PCC 6803. , 2006, DNA research : an international journal for rapid publication of reports on genes and genomes.

[67]  P. Lindblad,et al.  Hydrogenases in Nostoc sp. Strain PCC 73102, a Strain Lacking a Bidirectional Enzyme , 1997, Applied and environmental microbiology.

[68]  P. Lindblad,et al.  Occurrence and localization of an uptake hydrogenase in the filamentous heterocystous cyanobacteriumNostoc PCC 73102 , 1990, Protoplasma.

[69]  J. Guest,et al.  FNR and its role in oxygen-regulated gene expression in Escherichia coli. , 1990, FEMS microbiology reviews.

[70]  J. Lamerdin,et al.  An overview of the genome of Nostoc punctiforme, a multicellular, symbiotic cyanobacterium , 2004, Photosynthesis Research.

[71]  R. Srivastava,et al.  Proteomic studies of the thylakoid membrane of Synechocystis sp. PCC 6803 , 2005, Proteomics.

[72]  T. Jansén,et al.  Proteomic analysis of heterotrophy in Synechocystis sp. PCC 6803 , 2006, Proteomics.

[73]  Friedrich Lottspeich,et al.  Taming of a Poison: Biosynthesis of the NiFe-Hydrogenase Cyanide Ligands , 2003, Science.

[74]  Z. Chen,et al.  Characterization of a HoxEFUYH type of [NiFe] hydrogenase from Allochromatium vinosum and some EPR and IR properties of the hydrogenase module , 2006, JBIC Journal of Biological Inorganic Chemistry.

[75]  A. Melis,et al.  Development of the light-harvesting chlorophyll antenna in the green alga Chlamydomonas reinhardtii is regulated by the novel Tla1 gene , 2007, Planta.

[76]  M. Asayama,et al.  Highly repetitive sequences and characteristics of genomic DNA in unicellular cyanobacterial strains. , 1996, FEMS microbiology letters.

[77]  A. Böck,et al.  Characterisation of a protease from Escherichia coli involved in hydrogenase maturation. , 1995, European journal of biochemistry.

[78]  H. Bothe,et al.  Unusual Gene Arrangement of the Bidirectional Hydrogenase and Functional Analysis of Its Diaphorase Subunit HoxU in Respiration of the Unicellular Cyanobacterium Anacystis nidulans , 1998, Current Microbiology.

[79]  J. Appel,et al.  LexA regulates the bidirectional hydrogenase in the cyanobacterium Synechocystis sp. PCC 6803 as a transcription activator , 2005, Molecular microbiology.

[80]  I. Suzuki,et al.  Osmotic shrinkage of cells of Synechocystis sp. PCC 6803 by water efflux via aquaporins regulates osmostress-inducible gene expression. , 2005, Microbiology.

[81]  S. Mikkat,et al.  Proteome analysis of salt stress response in the cyanobacterium Synechocystis sp. strain PCC 6803 , 2006, Proteomics.

[82]  P. Lindblad,et al.  The bidirectional hydrogenase in the cyanobacterium Synechocystis sp. strain PCC 6803 , 2006 .

[83]  R. Eady.  Structure−Function Relationships of Alternative Nitrogenases , 1996 .

[84]  J. Benemann,et al.  Characterization and partial purification of the reversible hydrogenase of Anabaena cylindrica , 1978 .

[85]  J. W. Golden,et al.  Programmed DNA Rearrangement of A Hydrogenase Gene During Anabaena Heterocyst Development , 1998 .

[86]  H. Bothe,et al.  The diaphorase subunit HoxU of the bidirectional hydrogenase as electron transferring protein in cyanobacterial respiration? , 1996, Naturwissenschaften.

[87]  N. Miyajima,et al.  Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC6803. I. Sequence features in the 1 Mb region from map positions 64% to 92% of the genome. , 1995, DNA research : an international journal for rapid publication of reports on genes and genomes.

[88]  F. Tabita,et al.  Nickel Control of Hydrogen Production and Uptake in Anabaena spp. Strains CA and 1F , 1984 .

[89]  H. Sakurai,et al.  High Photobiological Hydrogen Production Activity of a Nostoc sp. PCC 7422 Uptake Hydrogenase-Deficient Mutant with High Nitrogenase Activity , 2006, Marine Biotechnology.

[90]  J. W. Peters,et al.  Homologous and Heterologous Overexpression in Clostridium acetobutylicum and Characterization of Purified Clostridial and Algal Fe-Only Hydrogenases with High Specific Activities , 2005, Applied and Environmental Microbiology.

[91]  E. Leitão,et al.  Characterization and transcriptional analysis of hupSLW in Gloeothece sp. ATCC 27152: an uptake hydrogenase from a unicellular cyanobacterium. , 2004, Microbiology.

[92]  August Böck,et al.  HypF, a Carbamoyl Phosphate-converting Enzyme Involved in [NiFe] Hydrogenase Maturation* , 2002, The Journal of Biological Chemistry.

[93]  L. E. Mikheeva,et al.  Mutants of the Cyanobacterium Anabaena variabilis Altered in Hydrogenase Activities , 1995 .

[94]  A. Böck,et al.  The biosynthetic routes for carbon monoxide and cyanide in the Ni–Fe active site of hydrogenases are different , 2005, FEBS letters.

[95]  R. Ebright,et al.  Transcription activation by catabolite activator protein (CAP). , 1999, Journal of molecular biology.

[96]  Jeff Shrager,et al.  Consequences of a Deletion in dspA on Transcript Accumulation in Synechocystis sp. Strain PCC6803 , 2004, Journal of bacteriology.

[97]  R. Burris,et al.  Comparative characterization of two distinct hydrogenases from Anabaena sp. strain 7120 , 1981, Journal of bacteriology.

[98]  P. Böger,et al.  Pathways of hydrogen uptake in the cyanobacterium Nostoc muscorum , 1985, Archives of Microbiology.

[99]  P. Lindblad,et al.  hupS and hupL constitute a transcription unit in the cyanobacterium Nostoc sp. PCC 73102 , 2000, Archives of Microbiology.

[100]  J. Meeks,et al.  A soluble 3D LC/MS/MS proteome of the filamentous cyanobacterium Nostoc punctiforme. , 2006, Journal of proteome research.

[101]  B. Bergman,et al.  REEVALUATION OF THE NITROGEN FIXATION BEHAVIOR IN THE MARINE NON‐HETEROCYSTOUS CYANOBACTERIUM LYNGBYA MAJUSCULA 1 , 2003 .

[102]  Anca M. Segall,et al.  In Vitro Selection of Integration Host Factor Binding Sites , 1999, Journal of bacteriology.

[103]  P. Lindblad,et al.  Hydrogen, uptake in Nostoc strain PCC 73102 : effects of nickel, hydrogen, carbon and nitrogen , 1995 .

[104]  A. Böck,et al.  Metal insertion into NiFe-hydrogenases. , 2001, Biochemical Society transactions.

[105]  S. Miyagishima.  Origin and evolution of the chloroplast division machinery , 2005, Journal of Plant Research.

[106]  I. Suzuki,et al.  Proteomic analysis of the heat shock response in Synechocystis PCC6803 and a thermally tolerant knockout strain lacking the histidine kinase 34 gene , 2006, Proteomics.

[107]  T. Happe,et al.  Transcriptional and Mutational Analysis of the Uptake Hydrogenase of the Filamentous CyanobacteriumAnabaena variabilis ATCC 29413 , 2000, Journal of bacteriology.

[108]  H. Sakurai,et al.  Promoting R & D in Photobiological Hydrogen Production Utilizing Mariculture-Raised Cyanobacteria , 2007, Marine Biotechnology.

[109]  August Böck,et al.  The complex between hydrogenase-maturation proteins HypC and HypD is an intermediate in the supply of cyanide to the active site iron of [NiFe]-hydrogenases. , 2004, Journal of molecular biology.

[110]  A. Böck,et al.  Analysis of the HypC-HycE Complex, a Key Intermediate in the Assembly of the Metal Center of the Escherichia coliHydrogenase 3* , 2000, The Journal of Biological Chemistry.

[111]  A. Böck,et al.  The hyp operon gene products are required for the maturation of catalytically active hydrogenase isoenzymes in Escherichia coli , 2004, Archives of Microbiology.

[112]  W. Vermaas,et al.  Subunits of the NAD(P)-Reducing Nickel-Containing Hydrogenase Do Not Act as Part of theType-1 NAD(P)H-Dehydrogenase in the Cyanobacterium Synechocystis sp. PCC 6803 , 1999 .

[113]  Juergen E. W. Polle,et al.  tla1, a DNA insertional transformant of the green alga Chlamydomonas reinhardtii with a truncated light-harvesting chlorophyll antenna size , 2003, Planta.

[114]  I. Suzuki,et al.  Metal dependence and intracellular regulation of the bidirectional NiFe-hydrogenase in Synechocystis sp. PCC 6803 , 2006 .

[115]  P. Lindblad,et al.  H2-Uptake and evolution in the unicellular cyanobacterium Chroococcidiopsis thermalis CALU 758 , 2000 .

[116]  H. Böhme.  Regulation of nitrogen fixation in heterocyst-forming cyanobacteria , 1998 .

[117]  Laurens Mets,et al.  Improvement of photosynthetic CO2 fixation at high light intensity through reduction of chlorophyll antenna size , 2002 .

[118]  A. Böck,et al.  Molecular characterization of an operon (hyp) necessary for the activity of the three hydrogenase isoenzymes in Escherichia coli , 1991, Molecular microbiology.

[119]  P. Lindblad,et al.  Evidence against a common use of the diaphorase subunits by the bidirectional hydrogenase and by the respiratory complex I in cyanobacteria , 1999 .

[120]  August Böck,et al.  Maturation of hydrogenases. , 2006, Advances in microbial physiology.

[121]  M. Adams,et al.  The structure and mechanism of iron-hydrogenases. , 1990, Biochimica et biophysica acta.

[122]  R. Huber,et al.  [NiFe]-Hydrogenase maturation endopeptidase: structure and function. , 2005, Biochemical Society transactions.

[123]  Peter Lindblad,et al.  Production of H2 by the unicellular cyanobacterium Gloeocapsa alpicola CALU 743 during fermentation , 2002 .

[124]  John R. Benemann,et al.  Dunaliella salina (Chlorophyta) with small chlorophyll antenna sizes exhibit higher photosynthetic productivities and photon use efficiencies than normally pigmented cells , 1998, Journal of Applied Phycology.

[125]  J. Guest,et al.  FNR and its role in oxygen-regulated gene expression in Escherichia coli , 1990 .

[126]  M. Mimuro,et al.  Complete genome structure of Gloeobacter violaceus PCC 7421, a cyanobacterium that lacks thylakoids. , 2003, DNA research : an international journal for rapid publication of reports on genes and genomes.

[127]  P. Lindblad,et al.  Transcriptional Regulation of Nostoc Hydrogenases: Effects of Oxygen, Hydrogen, and Nickel , 2002, Applied and Environmental Microbiology.

[128]  H. Sakurai,et al.  Disruption of the uptake hydrogenase gene, but not of the bidirectional hydrogenase gene, leads to enhanced photobiological hydrogen production by the nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 , 2002, Applied Microbiology and Biotechnology.

[129]  Minoru Kanehisa,et al.  Global Analysis of Circadian Expression in the Cyanobacterium Synechocystis sp. Strain PCC 6803 , 2005, Journal of bacteriology.

[130]  P. Lindblad,et al.  Hydrogen uptake in Nostoc sp. strain PCC 73102. Cloning and characterization of a hupSL homologue , 1998, Archives of Microbiology.

[131]  B. Bergman,et al.  Immunogold localization of hydrogenase in the cyanobacterial-plant symbioses Peltigera canina, Anthoceros punctatus and Gunnera magellanica , 1992 .

[132]  Y. Asada,et al.  Hydrogenase from the unicellular cyanobacterium, Microcystis aeruginosa , 1987 .

[133]  A. Böck,et al.  Dissection of the maturation reactions of the [NiFe] hydrogenase 3 from Escherichia coli taking place after nickel incorporation , 2000, FEBS letters.

[134]  A. Daday,et al.  The effect of nickel on hydrogen metabolism and nitrogen fixation in the cyanobacterium Anabaena cylindrica , 1985 .

[135]  Paulette M. Vignais,et al.  Sustained Photoevolution of Molecular Hydrogen in a Mutant of Synechocystis sp. Strain PCC 6803 Deficient in the Type I NADPH-Dehydrogenase Complex , 2004, Journal of bacteriology.

[136]  R. Hausinger,et al.  Biosynthesis of metal sites. , 2004, Chemical reviews.

[137]  R. Ueda,et al.  Improvement of photosynthesis in dense microalgal suspension by reduction of light harvesting pigments , 1997, Journal of Applied Phycology.

[138]  Haroon S. Kheshgi,et al.  The Photobiological Production of Hydrogen: Potential Efficiency and Effectiveness as a Renewable Fuel , 2005, Critical reviews in microbiology.

[139]  R. Hausinger,et al.  Nickel uptake and utilization by microorganisms. , 2003, FEMS microbiology reviews.

[140]  Y. Nakamura,et al.  Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC6803. II. Sequence determination of the entire genome and assignment of potential protein-coding regions (supplement). , 1996, DNA research : an international journal for rapid publication of reports on genes and genomes.

[141]  Michael Seibert,et al.  Discovery of Two Novel Radical S-Adenosylmethionine Proteins Required for the Assembly of an Active [Fe] Hydrogenase* , 2004, Journal of Biological Chemistry.

[142]  J. Gallon,et al.  Synthesis and proteolytic degradation of nitrogenase in cultures of the unicellular cyanobacterium Gloeothece strain ATCC 27152. , 1999, Microbiology.

[143]  F. Lottspeich,et al.  Molecular biological analysis of a bidirectional hydrogenase from cyanobacteria. , 1995, European journal of biochemistry.

[144]  R. Burris,et al.  Occurrence and localization of two distinct hydrogenases in the heterocystous cyanobacterium Anabaena sp. strain 7120 , 1981, Journal of bacteriology.

[145]  L. Casalot,et al.  Maturation of the [NiFe] hydrogenases. , 2001, Trends in microbiology.

[146]  P. Vignais,et al.  Molecular biology of microbial hydrogenases. , 2004, Current issues in molecular biology.

[147]  T. Happe,et al.  HoxE--a subunit specific for the pentameric bidirectional hydrogenase complex (HoxEFUYH) of cyanobacteria. , 2002, Biochimica et biophysica acta.

[148]  Maturation of [NiFe]-hydrogenases in Escherichia coli: the HypC cycle. , 2002, Journal of molecular biology.

[149]  Enrique Flores,et al.  Cellular differentiation and the NtcA transcription factor in filamentous cyanobacteria. , 2004, FEMS microbiology reviews.

[150]  H. Bothe,et al.  Quantitative analysis of expression of two circadian clock‐controlled gene clusters coding for the bidirectional hydrogenase in the cyanobacterium Synechococcus sp. PCC7942 , 2001, Molecular microbiology.

[151]  H. D. Kumar,et al.  Effect of monochromatic lights on nitrogen fixation and hydrogen evolution in the isolated heterocysts of Anabaena sp. strain CA , 1991 .

[152]  H. Bothe,et al.  Transcriptional Analysis of Hydrogenase Genes in the Cyanobacteria Anacystis nidulans and Anabaena variabilis Monitored by RT-PCR , 2000, Current Microbiology.

[153]  Ho-Sung Yoon,et al.  Heterocyst development in Anabaena. , 2003, Current opinion in microbiology.

[154]  Y. Nakamura,et al.  Complete genomic sequence of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120. , 2001, DNA research : an international journal for rapid publication of reports on genes and genomes.

[155]  W. McClure,et al.  Searching for and predicting the activity of sites for DNA binding proteins: compilation and analysis of the binding sites for Escherichia coli integration host factor (IHF). , 1990, Nucleic acids research.

[156]  C. D. de Koster,et al.  The Soluble NAD+-Reducing [NiFe]-Hydrogenase from Ralstonia eutropha H16 Consists of Six Subunits and Can Be Specifically Activated by NADPH , 2005, Journal of bacteriology.

[157]  Lawrence Pitt,et al.  Biohydrogen production: prospects and limitations to practical application , 2004 .

[158]  A. Böck,et al.  GTP hydrolysis by HypB is essential for nickel insertion into hydrogenases of Escherichia coli. , 1995, European journal of biochemistry.

[159]  Hong Li,et al.  Microarray analysis and redox control of gene expression in the cyanobacterium Synechocystis sp. PCC 6803. , 2004, Physiologia plantarum.

[160]  P. Lindblad,et al.  Identification of hox genes and analysis of their transcription in the unicellular cyanobacterium Gloeocapsa alpicola CALU 743 growing under nitrate-limiting conditions. , 2002, FEMS microbiology letters.

[161]  Cloning and characterisation of a hyp gene cluster in the filamentous cyanobacterium Nostoc sp. strain PCC 73102. , 2001, FEMS microbiology letters.

[162]  K. Shanmugam,et al.  Cloning, sequencing, and mutational analysis of the hyb operon encoding Escherichia coli hydrogenase 2 , 1994, Journal of bacteriology.

[163]  A. Böck,et al.  Generation of active [NiFe] hydrogenase in vitro from a nickel-free precursor form. , 1996, Biochemistry.

[164]  M. Maeda,et al.  Photoinduced Hydrogen Production by Direct Electron Transfer from Photosystem I Cross-Linked with Cytochrome c3 to [NiFe]-Hydrogenase , 2006, Photochemistry and photobiology.

[165]  R. Haselkorn,et al.  Inactivation of patS and hetN causes lethal levels of heterocyst differentiation in the filamentous cyanobacterium Anabaena sp. PCC 7120 , 2005, Molecular microbiology.

[166]  J. Appel,et al.  Mutagenesis of hydrogenase accessory genes of Synechocystis sp. PCC 6803 , 2006, The FEBS journal.

[167]  Michael Y. Galperin,et al.  The cyanobacterial genome core and the origin of photosynthesis , 2006, Proceedings of the National Academy of Sciences.

[168]  Paula Tamagnini,et al.  Diversity of Cyanobacterial Hydrogenases, a Molecular Approach , 2000, Current Microbiology.

[169]  A. Ernst,et al.  Heterocyst Metabolism and Development , 1994 .

[170]  G. Maróti,et al.  Cyanobacterial-Type, Heteropentameric, NAD+-Reducing NiFe Hydrogenase in the Purple Sulfur Photosynthetic Bacterium Thiocapsa roseopersicina , 2004, Applied and Environmental Microbiology.

[171]  Ying Zhao,et al.  Diversity of Nitrogenase Systems in Diazotrophs , 2006 .

[172]  D. Hall,et al.  Isolation and characterization of the hydrogenase activity from the non‐heterocystous cyanobacterium Spirulina maxima , 1979, FEBS letters.

[173]  E. Leitão,et al.  Analysis of the hupSL Operon of the Nonheterocystous Cyanobacterium Lyngbya majuscula CCAP 1446/4: Regulation of Transcription and Expression under a Light-Dark Regimen , 2005, Applied and Environmental Microbiology.

[174]  A. Böck,et al.  The product of the hypB gene, which is required for nickel incorporation into hydrogenases, is a novel guanine nucleotide-binding protein , 1993, Journal of bacteriology.

[175]  R. Haselkorn,et al.  Expression of the Anabaena hetR gene from a copper-regulated promoter leads to heterocyst differentiation under repressing conditions , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[176]  Heping Dai,et al.  Recent Aspects on the Hydrogenase-Nitrogenase Relationship in Cyanobacteria , 1991 .

[177]  J. W. Golden,et al.  Programmed DNA rearrangement of a cyanobacterial hupL gene in heterocysts. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[178]  A. Muro-Pastor,et al.  Nitrogen Control in Cyanobacteria , 2001, Journal of bacteriology.

[179]  A. Böck,et al.  Carbamoylphosphate requirement for synthesis of the active center of [NiFe]‐hydrogenases , 2001, FEBS letters.

[180]  N. Craig,et al.  E. coli integration host factor binds to specific sites in DNA , 1984, Cell.