Rewiring of Cyanobacterial Metabolism for Hydrogen Production: Synthetic Biology Approaches and Challenges

  • Anagha Krishnan
  • Xiao Qian
  • Gennady Ananyev
  • Desmond S. Lun
  • G. Charles DismukesEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1080)


With the demand for renewable energy growing, hydrogen (H2) is becoming an attractive energy carrier. Developing H2 production technologies with near-net zero carbon emissions is a major challenge for the “H2 economy.” Certain cyanobacteria inherently possess enzymes, nitrogenases, and bidirectional hydrogenases that are capable of H2 evolution using sunlight, making them ideal cell factories for photocatalytic conversion of water to H2. With the advances in synthetic biology, cyanobacteria are currently being developed as a “plug and play” chassis to produce H2. This chapter describes the metabolic pathways involved and the theoretical limits to cyanobacterial H2 production and summarizes the metabolic engineering technologies pursued.


BioH2 Bioenergy Biofuel Cyanobacteria Hydrogenase Nitrogenase Dark fermentation Photobiological H2 Metabolism Synthetic biology Metabolic engineering Hight-throughput screen 



GCD expresses his gratitude to former students and coworkers whose work provided some of the content summarized herein.


  1. 1.
    Joseck F, Nguyen T, Klahr B, Talapatra A (2016) In: D.o. energy (ed) DOE hydrogen and fuel cells program recordGoogle Scholar
  2. 2.
    Yi KB, Harrison DP (2005) Low-pressure sorption-enhanced hydrogen production. Ind Eng Chem Res 44:1665–1669CrossRefGoogle Scholar
  3. 3.
    Das D, Veziroǧlu TN (2001) Hydrogen production by biological processes: a survey of literature. Int J Hydrog Energy 26:13–28CrossRefGoogle Scholar
  4. 4.
    Whitton BA, Potts M (2007) The ecology of cyanobacteria: their diversity in time and space. Springer Science & Business MediaGoogle Scholar
  5. 5.
    Seckbach J (2007) Cellular origin, life in extreme habitats and astrobiology v. 11 1 online resource (xxxiv, 811 p.). Springer, DordrechtGoogle Scholar
  6. 6.
    Stal LJ (2015) In: Gargaud M et al (eds) Encyclopedia of astrobiology. Springer, Berlin, pp 595–599CrossRefGoogle Scholar
  7. 7.
    Mandal S, Rath J (2014) Extremophilic cyanobacteria for novel drug development. Springer International Publishing AG, ChamGoogle Scholar
  8. 8.
    Stal L (2015) Nitrogen fixation in cyanobacteria. eLS 1–9Google Scholar
  9. 9.
    Stal LJ, Moezelaar R (1997) Fermentation in cyanobacteria. FEMS Microbiol Rev 21:179–211CrossRefGoogle Scholar
  10. 10.
    Kumar D, Kumar HD (1992) Hydrogen production by several cyanobacteria. Int J Hydrog Energy 17:847–852CrossRefGoogle Scholar
  11. 11.
    Kothari A, Potrafka R, Garcia-Pichel F (2012) Diversity in hydrogen evolution from bidirectional hydrogenases in cyanobacteria from terrestrial, freshwater and marine intertidal environments. J Biotechnol 162:105–114PubMedCrossRefGoogle Scholar
  12. 12.
    Allahverdiyeva Y et al (2010) Screening for biohydrogen production by cyanobacteria isolated from the Baltic Sea and Finnish lakes. Int J Hydrog Energy 35:1117–1127CrossRefGoogle Scholar
  13. 13.
    Dutta D, De D, Chaudhuri S, Bhattacharya SK (2005) Hydrogen production by Cyanobacteria. Microb Cell Factories 4:36CrossRefGoogle Scholar
  14. 14.
    Leino H et al (2014) Characterization of ten H2 producing cyanobacteria isolated from the Baltic Sea and Finnish lakes. Int J Hydrog Energy 39:8983–8991CrossRefGoogle Scholar
  15. 15.
    Nielsen M, Revsbech NP, Kuhl M (2015) Microsensor measurements of hydrogen gas dynamics in cyanobacterial microbial mats. Front Microbiol 6:726PubMedPubMedCentralGoogle Scholar
  16. 16.
    Burow LC et al (2012) Hydrogen production in photosynthetic microbial mats in the Elkhorn Slough estuary, Monterey Bay. ISME J 6:863–874PubMedCrossRefGoogle Scholar
  17. 17.
    Happe T, Schutz K, Bohme H (2000) Transcriptional and mutational analysis of the uptake hydrogenase of the filamentous cyanobacterium Anabaena variabilis ATCC 29413. J Bacteriol 182:1624–1631PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Sveshnikov D, Sveshnikova N, Rao K, Hall D (1997) Hydrogen metabolism of mutant forms of Anabaena variabilis in continuous cultures and under nutritional stress. FEMS Microbiol Lett 147:297–301CrossRefGoogle Scholar
  19. 19.
    Cournac L, Guedeney G, Peltier G, Vignais PM (2004) Sustained photoevolution of molecular hydrogen in a mutant of Synechocystis sp. strain PCC 6803 deficient in the type I NADPH-dehydrogenase complex. J Bacteriol 186:1737–1746PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Bandyopadhyay A, Stockel J, Min H, Sherman LA, Pakrasi HB (2010) High rates of photobiological H2 production by a cyanobacterium under aerobic conditions. Nat Commun 1:139PubMedCrossRefGoogle Scholar
  21. 21.
    Troshina O, Serebryakova L, Sheremetieva M, Lindblad P (2002) Production of H2 by the unicellular cyanobacterium Gloeocapsa alpicola CALU 743 during fermentation. Int J Hydrog Energy 27:1283–1289CrossRefGoogle Scholar
  22. 22.
    Ananyev G, Carrieri D, Dismukes GC (2008) Optimization of metabolic capacity and flux through environmental cues to maximize hydrogen production by the cyanobacterium “Arthrospira (Spirulina) maxima”. Appl Environ Microbiol 74:6102–6113PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Huesemann MH, Hausmann TS, Carter BM, Gerschler JJ, Benemann JR (2010) Hydrogen generation through indirect biophotolysis in batch cultures of the nonheterocystous nitrogen-fixing cyanobacterium Plectonema boryanum. Appl Biochem Biotechnol 162:208–220PubMedCrossRefGoogle Scholar
  24. 24.
    Berla BM et al (2013) Synthetic biology of cyanobacteria: unique challenges and opportunities. Front Microbiol 4:246PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Camsund D, Lindblad P (2014) Engineered transcriptional systems for cyanobacterial biotechnology. Front Bioeng Biotechnol 2:40PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Pinto F et al (2012) Construction of a chassis for hydrogen production: physiological and molecular characterization of a Synechocystis sp. PCC 6803 mutant lacking a functional bidirectional hydrogenase. Microbiology 158:448–464PubMedCrossRefGoogle Scholar
  27. 27.
    Al-Haj L, Lui YT, Abed RM, Gomaa MA, Purton S (2016) Cyanobacteria as Chassis for industrial biotechnology: progress and prospects. Life (Basel) 6Google Scholar
  28. 28.
    Gao X, Sun T, Pei G, Chen L, Zhang W (2016) Cyanobacterial chassis engineering for enhancing production of biofuels and chemicals. Appl Microbiol Biotechnol 100:3401–3413PubMedCrossRefGoogle Scholar
  29. 29.
    Peter AP et al (2015) Cyanobacterial KnowledgeBase (CKB), a compendium of cyanobacterial genomes and proteomes. PLoS One 10:e0136262PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Nakao M et al (2010) CyanoBase: the cyanobacteria genome database update 2010. Nucleic Acids Res 38:D379–D381PubMedCrossRefGoogle Scholar
  31. 31.
    Ludwig M, Bryant DA (2011) Transcription profiling of the model cyanobacterium Synechococcus sp. strain PCC 7002 by next-gen (SOLiD) sequencing of cDNA. Front Microbiol 2:41PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Choi SY et al (2016) Transcriptome landscape of Synechococcus elongatus PCC 7942 for nitrogen starvation responses using RNA-seq. Sci Rep 6:30584PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Vijayan V, Jain IH, O'Shea EK (2011) A high resolution map of a cyanobacterial transcriptome. Genome Biol 12:R47PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kopf M et al (2014) Comparative analysis of the primary transcriptome of Synechocystis sp. PCC 6803. DNA Res 21:527–539PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Atsumi S, Higashide W, Liao JC (2009) Direct photosynthetic recycling of carbon dioxide to isobutyraldehyde. Nat Biotechnol 27:1177–1180PubMedCrossRefGoogle Scholar
  36. 36.
    Ruffing AM (2013) Borrowing genes from Chlamydomonas reinhardtii for free fatty acid production in engineered cyanobacteria. J Appl Phycol 25:1495–1507CrossRefGoogle Scholar
  37. 37.
    Dexter J, Fu P (2009) Metabolic engineering of cyanobacteria for ethanol production. Energy Environ Sci 2:857–864CrossRefGoogle Scholar
  38. 38.
    Lindberg P, Park S, Melis A (2010) Engineering a platform for photosynthetic isoprene production in cyanobacteria, using Synechocystis as the model organism. Metab Eng 12:70–79PubMedCrossRefGoogle Scholar
  39. 39.
    Wang W, Liu X, Lu X (2013) Engineering cyanobacteria to improve photosynthetic production of alka (e) nes. Biotechnol Biofuels 6:69PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Davies FK, Work VH, Beliaev AS, Posewitz MC (2014) Engineering limonene and bisabolene production in wild type and a glycogen-deficient mutant of Synechococcus sp. PCC 7002. Frontiers in bioengineering and biotechnology 2:21PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Xu Y et al (2013) Altered carbohydrate metabolism in glycogen synthase mutants of Synechococcus sp. strain PCC 7002: cell factories for soluble sugars. Metab Eng 16:56–67PubMedCrossRefGoogle Scholar
  42. 42.
    Xu Y et al (2011) Expression of genes in cyanobacteria: adaptation of endogenous plasmids as platforms for high-level gene expression in Synechococcus sp. PCC 7002. Methods Mol Biol 684:273–293PubMedCrossRefGoogle Scholar
  43. 43.
    Masukawa H, Mochimaru M, Sakurai H (2002) 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. Appl Microbiol Biotechnol 58:618–624PubMedCrossRefGoogle Scholar
  44. 44.
    Cai YA, Murphy JT, Wedemayer GJ, Glazer AN (2001) Recombinant phycobiliproteins. Recombinant C-phycocyanins equipped with affinity tags, oligomerization, and biospecific recognition domains. Anal Biochem 290:186–204PubMedCrossRefGoogle Scholar
  45. 45.
    Ren L, Shi D, Dai J, Ru B (1998) Expression of the mouse metallothionein-I gene conferring cadmium resistance in a transgenic cyanobacterium. FEMS Microbiol Lett 158:127–132PubMedCrossRefGoogle Scholar
  46. 46.
    Yu J et al (2015) Synechococcus elongatus UTEX 2973, a fast growing cyanobacterial chassis for biosynthesis using light and CO(2). Sci Rep 5:8132PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Schwarz D, Orf I, Kopka J, Hagemann M (2013) Recent applications of metabolomics toward cyanobacteria. Metabolites 3:72–100PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Saha R et al (2012) Reconstruction and comparison of the metabolic potential of cyanobacteria Cyanothece sp. ATCC 51142 and Synechocystis sp. PCC 6803. PLoS One 7(e48285)Google Scholar
  49. 49.
    Nogales J, Gudmundsson S, Knight EM, Palsson BO, Thiele I (2012) Detailing the optimality of photosynthesis in cyanobacteria through systems biology analysis. P Natl Acad Sci USA 109:2678–2683CrossRefGoogle Scholar
  50. 50.
    Montagud A, Navarro E, Fernandez de Cordoba P, Urchueguia JF, Patil KR (2010) Reconstruction and analysis of genome-scale metabolic model of a photosynthetic bacterium. BMC Syst Biol 4:156PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Shastri AA, Morgan JA (2005) Flux balance analysis of photoautotrophic metabolism. Biotechnol Prog 21:1617–1626PubMedCrossRefGoogle Scholar
  52. 52.
    Knoop H, Zilliges Y, Lockau W, Steuer R (2010) The metabolic network of Synechocystis sp. PCC 6803: systemic properties of autotrophic growth. Plant Physiol 154:410–422PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Yoshikawa K et al (2011) Reconstruction and verification of a genome-scale metabolic model for Synechocystis sp. PCC6803. Appl Microbiol Biotechnol 92:347–358PubMedCrossRefGoogle Scholar
  54. 54.
    Vu TT et al (2013) Computational evaluation of Synechococcus sp. PCC 7002 metabolism for chemical production. Biotechnol J 8:619–630PubMedCrossRefGoogle Scholar
  55. 55.
    Qian X et al (2017) Flux balance analysis of photoautotrophic metabolism: uncovering new biological details of subsystems involved in cyanobacterial photosynthesis. Biochim Biophys Acta 1858:276–287PubMedCrossRefGoogle Scholar
  56. 56.
    Vu TT et al (2012) Genome-scale modeling of light-driven reductant partitioning and carbon fluxes in diazotrophic unicellular cyanobacterium Cyanothece sp. ATCC 51142. PLoS Comput Biol 8:e1002460PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Alagesan S, Gaudana SB, Sinha A, Wangikar PP (2013) Metabolic flux analysis of Cyanothece sp. ATCC 51142 under mixotrophic conditions. Photosynth Res 118:191–198PubMedCrossRefGoogle Scholar
  58. 58.
    Klanchui A, Khannapho C, Phodee A, Cheevadhanarak S, Meechai A (2012) iAK692: a genome-scale metabolic model of Spirulina platensis C1. BMC Syst Biol 6:71PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Beck AE, Bernstein HC, Carlson RP (2017) Stoichiometric network analysis of cyanobacterial acclimation to photosynthesis-associated stresses identifies heterotrophic niches. PRO 5:32Google Scholar
  60. 60.
    Yamasato A, Satoh K (2001) The establishment of conditions to efficiently screen photosynthesis-deficient mutants of Synechocystis sp. PCC 6803 by nitrofurantoin treatment. Plant Cell Physiol 42:414–418PubMedCrossRefGoogle Scholar
  61. 61.
    Ortega-Ramos M et al (2014) Engineering Synechocystis PCC6803 for hydrogen production: influence on the tolerance to oxidative and sugar stresses. PLoS One 9:e89372PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Anderson SL, McIntosh L (1991) Light-activated heterotrophic growth of the cyanobacterium Synechocystis sp. strain PCC 6803: a blue-light-requiring process. J Bacteriol 173:2761–2767PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Ducat DC, Sachdeva G, Silver PA (2011) Rewiring hydrogenase-dependent redox circuits in cyanobacteria. Proc Natl Acad Sci U S A 108:3941–3946PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Lindberg P, Schütz K, Happe T, Lindblad P (2002) A hydrogen-producing, hydrogenase-free mutant strain of Nostoc punctiforme ATCC 29133. Int J Hydrog Energy 27:1291–1296CrossRefGoogle Scholar
  65. 65.
    Yoshino F, Ikeda H, Masukawa H, Sakurai H (2007) High photobiological hydrogen production activity of a Nostoc sp. PCC 7422 uptake hydrogenase-deficient mutant with high nitrogenase activity. Mar Biotechnol (NY) 9:101–112CrossRefGoogle Scholar
  66. 66.
    Miyake J (1998) In: Zaborsky OR, Benemann JR, Matsunaga T, Miyake J, San Pietro A (eds) BioHydrogen. Springer US, Boston, pp 7–18Google Scholar
  67. 67.
    Chen M, Hiller RG, Howe CJ, Larkum AWD (2005) Unique origin and lateral transfer of prokaryotic chlorophyll-b and chlorophyll-d light-harvesting systems. Mol Biol Evol 22:21–28PubMedCrossRefGoogle Scholar
  68. 68.
    Chen M, Li YQ, Birch D, Willows RD (2012) A cyanobacterium that contains chlorophyll f – a red-absorbing photopigment. FEBS Lett 586:3249–3254PubMedCrossRefGoogle Scholar
  69. 69.
    Chen M, Blankenship RE (2011) Expanding the solar spectrum used by photosynthesis. Trends Plant Sci 16:427–431PubMedCrossRefGoogle Scholar
  70. 70.
    DOE (2015) In: U.S.o.A. Department of energy (ed) United States of AmericaGoogle Scholar
  71. 71.
    Tamagnini P et al (2007) Cyanobacterial hydrogenases: diversity, regulation and applications. FEMS Microbiol Rev 31:692–720PubMedCrossRefGoogle Scholar
  72. 72.
    Peters JW et al (2015) [FeFe]- and [NiFe]-hydrogenase diversity, mechanism, and maturation. BBA-Mol Cell Res 1853:1350–1369Google Scholar
  73. 73.
    Mulder DW et al (2011) Insights into [FeFe]-hydrogenase structure, mechanism, and maturation. Structure 19:1038–1052PubMedCrossRefGoogle Scholar
  74. 74.
    Carrieri D, Wawrousek K, Eckert C, Yu J, Maness PC (2011) The role of the bidirectional hydrogenase in cyanobacteria. Bioresour Technol 102:8368–8377PubMedCrossRefGoogle Scholar
  75. 75.
    Bothe H, Schmitz O, Yates MG, Newton WE (2010) Nitrogen fixation and hydrogen metabolism in cyanobacteria. Microbiol Mol Biol R 74:529–551CrossRefGoogle Scholar
  76. 76.
    Adams MW (1990) The structure and mechanism of iron-hydrogenases. Biochim Biophys Acta 1020:115–145PubMedCrossRefGoogle Scholar
  77. 77.
    Vignais PM, Billoud B, Meyer J (2001) Classification and phylogeny of hydrogenases. FEMS Microbiol Rev 25:455–501PubMedCrossRefGoogle Scholar
  78. 78.
    Hallenbeck PC, Benemann JR (2002) Biological hydrogen production; fundamentals and limiting processes. Int J Hydrog Energy 27:1185–1193CrossRefGoogle Scholar
  79. 79.
    Frey M (2002) Hydrogenases: hydrogen-activating enzymes. Chembiochem 3:153–160PubMedCrossRefGoogle Scholar
  80. 80.
    Barney BM, Yurth MG, Dos Santos PC, Dean DR, Seefeldt LC (2009) A substrate channel in the nitrogenase MoFe protein. J Biol Inorg Chem : JBIC : Publ Soc Biol Inorg Chem 14:1015CrossRefGoogle Scholar
  81. 81.
    Morrison CN, Hoy JA, Zhang L, Einsle O, Rees DC (2015) Substrate pathways in the nitrogenase MoFe protein by experimental identification of small molecule binding sites. Biochemistry 54:2052–2060PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Telor E, Stewart WDP (1977) Photosynthetic components and activities of nitrogen-fixing isolated heterocysts of Anabaena-cylindrica. Proc R Soc Ser B-Bio 198:61–86CrossRefGoogle Scholar
  83. 83.
    Golden JW, Yoon HS (2003) Heterocyst development in Anabaena. Curr Opin Microbiol 6:557–563PubMedCrossRefGoogle Scholar
  84. 84.
    Murry MA, Wolk CP (1989) Evidence that the barrier to the penetration of oxygen into heterocysts depends upon 2 layers of the cell-envelope. Arch Microbiol 151:469–474CrossRefGoogle Scholar
  85. 85.
    Berman-Frank I et al (2001) Segregation of nitrogen fixation and oxygenic photosynthesis in the marine cyanobacterium Trichodesmium. Science 294:1534–1537PubMedCrossRefGoogle Scholar
  86. 86.
    Kumar K, Das D (2013) In: Reazeghifard R (ed) Natural and artificial photosynthesis: solar power as an energy source, 1st edn. WileyGoogle Scholar
  87. 87.
    Hu Y, Lee CC, Ribbe MW (2012) Vanadium nitrogenase: a two-hit wonder? Dalton Trans (Cambridge, England : 2003) 41.
  88. 88.
    Steunou A-S et al (2008) Regulation of nif gene expression and the energetics of N2 fixation over the diel cycle in a hot spring microbial mat. ISME J 2:364–378PubMedCrossRefGoogle Scholar
  89. 89.
    Ludwig M, Schulz-Friedrich R, Appel J (2006) Occurrence of hydrogenases in cyanobacteria and anoxygenic photosynthetic bacteria: implications for the phylogenetic origin of cyanobacterial and algal hydrogenases. J Mol Evol 63:758–768PubMedCrossRefGoogle Scholar
  90. 90.
    Tamagnini P et al (2002) Hydrogenases and hydrogen metabolism of cyanobacteria. Microbiol Mol Biol Rev 66:1–20., table of contentsPubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Carrasco CD, Buettner JA, Golden JW (1995) Programmed DNA rearrangement of a cyanobacterial hupL gene in heterocysts. Proc Natl Acad Sci U S A 92:791–795PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Boison G, Bothe H, Schmitz O (2000) Transcriptional analysis of hydrogenase genes in the cyanobacteria Anacystis nidulans and Anabaena variabilis monitored by RT-PCR. Curr Microbiol 40:315–321PubMedCrossRefGoogle Scholar
  93. 93.
    Oliveira P, Leitao E, Tamagnini P, Moradas-Ferreira P, Oxelfelt F (2004) Characterization and transcriptional analysis of hupSLW in Gloeothece sp. ATCC 27152: an uptake hydrogenase from a unicellular cyanobacterium. Microbiology 150:3647–3655PubMedCrossRefGoogle Scholar
  94. 94.
    Axelsson R, Lindblad P (2002) Transcriptional regulation of Nostoc hydrogenases: effects of oxygen, hydrogen, and nickel. Appl Environ Microbiol 68:444–447PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Aubert-Jousset E, Cano M, Guedeney G, Richaud P, Cournac L (2011) Role of HoxE subunit in Synechocystis PCC6803 hydrogenase. FEBS J 278:4035–4043PubMedCrossRefGoogle Scholar
  96. 96.
    Ghirardi ML et al (2007) Hydrogenases and hydrogen photoproduction in oxygenic photosynthetic organisms. Annu Rev Plant Biol 58:71–91PubMedCrossRefGoogle Scholar
  97. 97.
    Gutekunst K et al (2014) The bidirectional NiFe-hydrogenase in Synechocystis sp. PCC 6803 is reduced by flavodoxin and ferredoxin and is essential under mixotrophic, nitrate-limiting conditions. J Biol Chem 289:1930–1937PubMedCrossRefGoogle Scholar
  98. 98.
    McIntosh CL, Germer F, Schulz R, Appel J, Jones AK (2011) The [NiFe]-hydrogenase of the cyanobacterium Synechocystis sp. PCC 6803 works bidirectionally with a bias to H2 production. J Am Chem Soc 133:11308–11319PubMedCrossRefGoogle Scholar
  99. 99.
    Stiebritz MT, Reiher M (2012) Hydrogenases and oxygen. Chem Sci 3:1739–1751CrossRefGoogle Scholar
  100. 100.
    Montet Y et al (1997) Gas access to the active site of Ni-Fe hydrogenases probed by X-ray crystallography and molecular dynamics. Nat Struct Biol 4:523–526PubMedCrossRefGoogle Scholar
  101. 101.
    Volbeda A, Fontecilla-Camps JC (2003) The active site and catalytic mechanism of NiFe hydrogenases. Dalton Trans 4030–4038Google Scholar
  102. 102.
    Volbeda A, Montet Y, Vernede X, Claude Hatchikian E, Fontecilla-Camps J (2002) High-resolution crystallographic analysis of Desulfovibrio fructosovorans [NiFe] hydrogenase. Int J Hydrogen Energy 27:1449–1461CrossRefGoogle Scholar
  103. 103.
    Ghirardi ML, Maness PC, Seibert M (2008) In: Rajeshwar K, McConnell R, Licht S (eds) Solar hydrogen generation: toward a renewable energy future. Springer, New York, pp 229–271CrossRefGoogle Scholar
  104. 104.
    Adamson H et al (2017) Retuning the catalytic bias and overpotential of a [NiFe]-hydrogenase via a single amino acid exchange at the electron entry/exit site. J Am Chem Soc 139:10677–10686PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Laursen AB et al (2015) Nanocrystalline Ni5P4: a hydrogen evolution electrocatalyst of exceptional efficiency in both alkaline and acidic media. Energy Environ Sci 8:1027–1034CrossRefGoogle Scholar
  106. 106.
    Posewitz MC et al (2004) Discovery of two novel radical S-adenosylmethionine proteins required for the assembly of an active [Fe] hydrogenase. J Biol Chem 279:25711–25720PubMedCrossRefGoogle Scholar
  107. 107.
    Kubas A et al (2017) Mechanism of O2 diffusion and reduction in FeFe hydrogenases. Nat Chem 9:88–95PubMedGoogle Scholar
  108. 108.
    Ananyev GM, Skizim NJ, Dismukes GC (2012) Enhancing biological hydrogen production from cyanobacteria by removal of excreted products. J Biotechnol 162:97–104PubMedCrossRefGoogle Scholar
  109. 109.
    Houchins JP (1984) The physiology and biochemistry of hydrogen metabolism in cyanobacteria. Biochim Biophys Acta (BBA) – Rev Bioenerg 768:227–255CrossRefGoogle Scholar
  110. 110.
    Appel J, Phunpruch S, Steinmüller K, Schulz R (2000) The bidirectional hydrogenase of Synechocystis sp. PCC 6803 works as an electron valve during photosynthesis. Arch Microbiol 173:333–338PubMedCrossRefGoogle Scholar
  111. 111.
    Skizim NJ, Ananyev GM, Krishnan A, Dismukes GC (2012) Metabolic pathways for photobiological hydrogen production by nitrogenase- and hydrogenase-containing unicellular cyanobacteria Cyanothece. J Biol Chem 287:2777–2786PubMedCrossRefGoogle Scholar
  112. 112.
    Kirilovsky D (2007) Photoprotection in cyanobacteria: the orange carotenoid protein (OCP)-related non-photochemical-quenching mechanism. Photosynth Res 93:7–16PubMedCrossRefGoogle Scholar
  113. 113.
    Mullineaux CW (2014) Co-existence of photosynthetic and respiratory activities in cyanobacterial thylakoid membranes. Biochim Biophys Acta 1837:503–511PubMedCrossRefGoogle Scholar
  114. 114.
    Kramer DM, Evans JR (2011) The importance of energy balance in improving photosynthetic productivity. Plant Physiol 155:70–78PubMedCrossRefGoogle Scholar
  115. 115.
    Shimakawa G et al (2017) Diverse strategies of O2 usage for preventing photo-oxidative damage under CO2 limitation during algal photosynthesis. Sci Rep 7:41022PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    La Rocca N, Moro I, Rascio N (2016) Handbook of photosynthesis, 3rd edn. CRC Press, Boca Raton, pp 369–396Google Scholar
  117. 117.
    Lea-Smith DJ, Bombelli P, Vasudevan R, Howe CJ (2016) Photosynthetic, respiratory and extracellular electron transport pathways in cyanobacteria. Biochim Biophys Acta 1857:247–255PubMedCrossRefGoogle Scholar
  118. 118.
    Allahverdiyeva Y, Isojarvi J, Zhang P, Aro EM (2015) Cyanobacterial oxygenic photosynthesis is protected by flavodiiron proteins. Life (Basel) 5:716–743Google Scholar
  119. 119.
    Flores E, Frias JE, Rubio LM, Herrero A (2005) Photosynthetic nitrate assimilation in cyanobacteria. Photosynth Res 83:117–133PubMedCrossRefGoogle Scholar
  120. 120.
    Navarro F, Martín-Figueroa E, Candau P, Florencio FJ (2000) Ferredoxin-dependent iron–sulfur flavoprotein glutamate synthase (GlsF) from the cyanobacterium Synechocystis sp. PCC 6803: expression and assembly in Escherichia coli. Arch Biochem Biophys 379:267–276PubMedCrossRefGoogle Scholar
  121. 121.
    Lea-Smith DJ et al (2013) Thylakoid terminal oxidases are essential for the cyanobacterium Synechocystis sp. PCC 6803 to survive rapidly changing light intensities. Plant Physiol 162:484–495PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Joliot P, Joliot A (2006) Cyclic electron flow in C3 plants. Biochim Biophys Acta 1757:362–368PubMedCrossRefGoogle Scholar
  123. 123.
    Hart SE, Schlarb-Ridley BG, Bendall DS, Howe CJ (2005) Terminal oxidases of cyanobacteria. Biochem Soc Trans 33:832–835PubMedCrossRefGoogle Scholar
  124. 124.
    Rakhimberdieva MG, Elanskaya IV, Vermaas WFJ, Karapetyan NV (2010) Carotenoid-triggered energy dissipation in phycobilisomes of Synechocystis sp. PCC 6803 diverts excitation away from reaction centers of both photosystems. Biochim Biophys Acta (BBA) – Bioenerg 1797:241–249CrossRefGoogle Scholar
  125. 125.
    Helman Y et al (2003) Genes encoding A-type flavoproteins are essential for photoreduction of O2 in cyanobacteria. Curr Biol 13:230–235PubMedCrossRefGoogle Scholar
  126. 126.
    Mustila H et al (2016) The flavodiiron protein Flv3 functions as a homo-oligomer during stress acclimation and is distinct from the Flv1/Flv3 hetero-oligomer specific to the O2 photoreduction pathway. Plant Cell Physiol 57:1468–1483PubMedPubMedCentralGoogle Scholar
  127. 127.
    Eisenhut M et al (2008) The photorespiratory glycolate metabolism is essential for cyanobacteria and might have been conveyed endosymbiontically to plants. Proc Natl Acad Sci 105:17199–17204PubMedCrossRefGoogle Scholar
  128. 128.
    Hishiya S et al (2008) Binary reducing equivalent pathways using NADPH-thioredoxin reductase and ferredoxin-thioredoxin reductase in the cyanobacterium Synechocystis sp. strain PCC 6803. Plant Cell Physiol 49:11–18PubMedCrossRefGoogle Scholar
  129. 129.
    Flores E, Herrero A (1994) In: Peschek GA, Loffelhardt W, Schmetterer G (eds) The molecular biology of cyanobacteria. Kluwer Academic, New YorkGoogle Scholar
  130. 130.
    Prince RC, Kheshgi HS (2005) The photobiological production of hydrogen: potential efficiency and effectiveness as a renewable fuel. Crit Rev Microbiol 31:19–31PubMedCrossRefGoogle Scholar
  131. 131.
    Kruse O, Rupprecht J, Mussgnug JH, Dismukes GC, Hankamer B (2005) Photosynthesis: a blueprint for solar energy capture and biohydrogen production technologies. Photochem Photobiol Sci 4:957–970PubMedCrossRefGoogle Scholar
  132. 132.
    Ort DR, Zhu XG, Melis A (2011) Optimizing antenna size to maximize photosynthetic efficiency. Plant Physiol 155:79–85PubMedCrossRefGoogle Scholar
  133. 133.
    Kok B (1956) Photosynthesis in flashing light. Biochim Biophys Acta 21:245–258PubMedCrossRefGoogle Scholar
  134. 134.
    Nakajima Y, Fujiwara S, Sawai H, Imashimizu M, Tsuzuki M (2001) A phycocyanin-deficient mutant of Synechocystis PCC 6714 with a single-base substitution upstream of the cpc Operon. Plant Cell Physiol 42:992–998PubMedCrossRefGoogle Scholar
  135. 135.
    Bernat G, Waschewski N, Rogner M (2009) Towards efficient hydrogen production: the impact of antenna size and external factors on electron transport dynamics in Synechocystis PCC 6803. Photosynth Res 99:205–216PubMedCrossRefGoogle Scholar
  136. 136.
    Ananyev G, Dismukes GC (2005) How fast can Photosystem II split water? Kinetic performance at high and low frequencies. Photosynth Res 84:355–365PubMedCrossRefGoogle Scholar
  137. 137.
    Allakhverdiev S et al. (2010) Photosynthetic energy conversion: hydrogen photoproduction by natural and biomimetic means.Google Scholar
  138. 138.
    Ohkawa H, Pakrasi HB, Ogawa T (2000) Two types of functionally distinct NAD(P)H dehydrogenases in Synechocystis sp. strain PCC6803. J Biol Chem 275:31630–31634PubMedCrossRefGoogle Scholar
  139. 139.
    Peschek GA, Obinger C, Paumann M (2004) The respiratory chain of blue-green algae (cyanobacteria). Physiol Plant 120:358–369PubMedCrossRefGoogle Scholar
  140. 140.
    Berger S, Ellersiek U, Steinmuller K (1991) Cyanobacteria contain a mitochondrial complex I-homologous NADH-dehydrogenase. FEBS Lett 286:129–132PubMedCrossRefGoogle Scholar
  141. 141.
    Alpes I, Scherer S, Böger P (1989) The respiratory NADH dehydrogenase of the cyanobacterium Anabaena variabilis: purification and characterization. Biochim Biophys Acta (BBA) – Bioenerg 973:41–46CrossRefGoogle Scholar
  142. 142.
    Ogawa T (1991) A gene homologous to the subunit-2 gene of NADH dehydrogenase is essential to inorganic carbon transport of Synechocystis PCC6803. Proc Natl Acad Sci U S A 88:4275–4279PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Cooley JW, Vermaas WF (2001) Succinate dehydrogenase and other respiratory pathways in thylakoid membranes of Synechocystis sp. strain PCC 6803: capacity comparisons and physiological function. J Bacteriol 183:4251–4258PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Belkin S, Padan E (1978) Sulfide-dependent hydrogen evolution in the cyanobacterium Oscillatoria limnetica. FEBS Lett 94:291–294CrossRefGoogle Scholar
  145. 145.
    Imashimizu M et al (2011) Regulation of F0F1-ATPase from Synechocystis sp. PCC 6803 by gamma and epsilon subunits is significant for light/dark adaptation. J Biol Chem 286:26595–26602PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Gutthann F, Egert M, Marques A, Appel J (2007) Inhibition of respiration and nitrate assimilation enhances photohydrogen evolution under low oxygen concentrations in Synechocystis sp. PCC 6803. Biochim Biophys Acta 1767:161–169PubMedCrossRefGoogle Scholar
  147. 147.
    Moezelaar R, Bijvank SM, Stal LJ (1996) Fermentation and sulfur reduction in the mat-building cyanobacterium Microcoleus chthonoplastes. Appl Environ Microbiol 62:1752–1758PubMedPubMedCentralGoogle Scholar
  148. 148.
    Kumaraswamy GK et al (2013) Reprogramming the glycolytic pathway for increased hydrogen production in cyanobacteria: metabolic engineering of NAD+-dependent GAPDH. Energy Environ Sci 6:3722–3731CrossRefGoogle Scholar
  149. 149.
    McNeely K, Xu Y, Bennette N, Bryant DA, Dismukes GC (2010) Redirecting reductant flux into hydrogen production via metabolic engineering of fermentative carbon metabolism in a cyanobacterium. Appl Environ Microbiol 76:5032–5038PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Guerra LT et al (2013) Natural osmolytes are much less effective substrates than glycogen for catabolic energy production in the marine cyanobacterium Synechococcus sp. strain PCC 7002. J Biotechnol 166:65–75PubMedCrossRefGoogle Scholar
  151. 151.
    Woodward J, Orr M, Cordray K, Greenbaum E (2000) Enzymatic production of biohydrogen. Nature 405:1014–1015PubMedCrossRefGoogle Scholar
  152. 152.
    Thauer RK, Jungermann K, Decker K (1977) Energy conservation in chemotrophic anaerobic bacteria. Bacteriol Rev 41:100–180PubMedPubMedCentralGoogle Scholar
  153. 153.
    Muro-Pastor MI, Reyes JC, Florencio FJ (2005) Ammonium assimilation in cyanobacteria. Photosynth Res 83:135–150PubMedCrossRefGoogle Scholar
  154. 154.
    Irmler A, Sanner S, Dierks H, Forchhammer K (1997) Dephosphorylation of the phosphoprotein P(II) in Synechococcus PCC 7942: identification of an ATP and 2-oxoglutarate-regulated phosphatase activity. Mol Microbiol 26:81–90PubMedCrossRefGoogle Scholar
  155. 155.
    Forchhammer K (1999) In: Peschek GA, Loffelhardt W, Schmetterer G (eds) The phototrophic prokaryotes. Kluwer Academic, New YorkGoogle Scholar
  156. 156.
    Herrero A, Muro-Pastor AM, Flores E (2001) Nitrogen control in cyanobacteria. J Bacteriol 183:411–425PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Klotz A, Reinhold E, Doello S, Forchhammer K (2015) Nitrogen starvation acclimation in Synechococcus elongatus: redox-control and the role of nitrate reduction as an electron sink. Life (Basel) 5:888–904Google Scholar
  158. 158.
    Schwarz R, Grossman AR (1998) A response regulator of cyanobacteria integrates diverse environmental signals and is critical for survival under extreme conditions. Proc Natl Acad Sci U S A 95:11008–11013PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Hickman JW et al (2013) Glycogen synthesis is a required component of the nitrogen stress response in Synechococcus elongatus PCC 7942. Algal Res 2:98–106CrossRefGoogle Scholar
  160. 160.
    Grundel M, Scheunemann R, Lockau W, Zilliges Y (2012) Impaired glycogen synthesis causes metabolic overflow reactions and affects stress responses in the cyanobacterium Synechocystis sp. PCC 6803. Microbiology 158:3032–3043PubMedCrossRefGoogle Scholar
  161. 161.
    Hasunuma T et al (2013) Dynamic metabolic profiling of cyanobacterial glycogen biosynthesis under conditions of nitrate depletion. J Exp Bot 64:2943–2954PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Salomon E, Bar-Eyal L, Sharon S, Keren N (2013) Balancing photosynthetic electron flow is critical for cyanobacterial acclimation to nitrogen limitation. Biochim Biophys Acta 1827:340–347PubMedCrossRefGoogle Scholar
  163. 163.
    Kumazawa S, Mitsui A (1994) Efficient hydrogen photoproduction by synchronously grown cells of a marine cyanobacterium, Synechococcus sp. Miami BG 043511, under high cell density conditions. Biotechnol Bioeng 44:854–858PubMedCrossRefGoogle Scholar
  164. 164.
    Sakurai H, Masukawa H, Kitashima M, Inoue K (2015) How close we are to achieving commercially viable large-scale photobiological hydrogen production by cyanobacteria: a review of the biological aspects. Life (Basel) 5:997–1018Google Scholar
  165. 165.
    Miyamoto K, Hallenbeck P, Benemann J (1979) Solar energy conversion by nitrogen-limited cultures of Anabaena cylindrica. J Ferment TechnolGoogle Scholar
  166. 166.
    Miyamoto K, Hallenbeck PC, Benemann JR (1979) Effects of nitrogen supply on hydrogen production by cultures of Anabaena cylindrica. Biotechnol Bioeng 21:1855–1860CrossRefGoogle Scholar
  167. 167.
    Melnicki MR et al (2012) Sustained H(2) production driven by photosynthetic water splitting in a unicellular cyanobacterium. MBio 3:e00197–e00112PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Lambert GR, Smith GD (1977) Hydrogen formation by marine blue-green algae. FEBS Lett 83:159–162PubMedCrossRefGoogle Scholar
  169. 169.
    Weissman JC, Benemann JR (1977) Hydrogen production by nitrogen-starved cultures of Anabaena cylindrica. Appl Environ Microbiol 33:123–131PubMedPubMedCentralGoogle Scholar
  170. 170.
    Lambert GR, Daday A, Smith GD (1979) Hydrogen evolution from immobilized cultures of the cyanobacterium Anabaena cylindrica B629. FEBS Lett 101:125–128PubMedCrossRefGoogle Scholar
  171. 171.
    Kumar K, Mella-Herrera RA, Golden JW (2010) Cyanobacterial heterocysts. Cold Spring Harb Perspect Biol 2:a000315PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Baebprasert W, Jantaro S, Khetkorn W, Lindblad P, Incharoensakdi A (2011) Increased H2 production in the cyanobacterium Synechocystis sp. strain PCC 6803 by redirecting the electron supply via genetic engineering of the nitrate assimilation pathway. Metab Eng 13:610–616PubMedCrossRefGoogle Scholar
  173. 173.
    McNeely K et al (2014) Metabolic switching of central carbon metabolism in response to nitrate: application to autofermentative hydrogen production in cyanobacteria. J Biotechnol 182–183C:83–91CrossRefGoogle Scholar
  174. 174.
    Qian X et al (2016) Inactivation of nitrate reductase alters metabolic branching of carbohydrate fermentation in the cyanobacterium Synechococcus sp. strain PCC 7002. Biotechnol Bioeng 113:979–988PubMedCrossRefGoogle Scholar
  175. 175.
    Schutz K et al (2004) Cyanobacterial H(2) production – a comparative analysis. Planta 218:350–359PubMedCrossRefGoogle Scholar
  176. 176.
    Khetkorn W, Lindblad P, Incharoensakdi A (2012) Inactivation of uptake hydrogenase leads to enhanced and sustained hydrogen production with high nitrogenase activity under high light exposure in the cyanobacterium Anabaena siamensis TISTR 8012. J Biol Eng 6:19PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Berman-Frank I, Lundgren P, Falkowski P (2003) Nitrogen fixation and photosynthetic oxygen evolution in cyanobacteria. Res Microbiol 154:157–164PubMedCrossRefGoogle Scholar
  178. 178.
    Masukawa H, Sakurai H, Hausinger RP, Inoue K (2017) Increased heterocyst frequency by patN disruption in Anabaena leads to enhanced photobiological hydrogen production at high light intensity and high cell density. Appl Microbiol Biotechnol 101:2177–2188PubMedCrossRefGoogle Scholar
  179. 179.
    Carrieri D et al (2010) Boosting autofermentation rates and product yields with sodium stress cycling: application to production of renewable fuels by cyanobacteria. Appl Environ Microbiol 76:6455–6462PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Song K, Tan X, Liang Y, Lu X (2016) The potential of Synechococcus elongatus UTEX 2973 for sugar feedstock production. Appl Microbiol Biotechnol 100:7865–7875PubMedCrossRefGoogle Scholar
  181. 181.
    Hagemann M (2011) Molecular biology of cyanobacterial salt acclimation. FEMS Microbiol Rev 35:87–123PubMedCrossRefGoogle Scholar
  182. 182.
    Shah V, Garg N, Madamwar D (2003) Ultrastructure of the cyanobacterium Nostoc muscorum and exploitation of the culture for hydrogen production. Folia Microbiol (Praha) 48:65–70CrossRefGoogle Scholar
  183. 183.
    Shah V, Garg N, Madamwar D (2001) Ultrastructure of the fresh water cyanobacterium Anabaena variabilis SPU 003 and its application for oxygen-free hydrogen production. FEMS Microbiol Lett 194:71–75PubMedCrossRefGoogle Scholar
  184. 184.
    Baebprasert W, Lindblad P, Incharoensakdi A (2010) Response of H2 production and Hox-hydrogenase activity to external factors in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803. Int J Hydrog Energy 35:6611–6616CrossRefGoogle Scholar
  185. 185.
    Kuwada Y, Ohta Y (1989) Hydrogen production and carbohydrate consumption by Lyngbya sp.(No. 108). Agric Biol Chem 53:2847–2851Google Scholar
  186. 186.
    Prabaharan D, Subramanian G (1996) Oxygen-free hydrogen production by the marine cyanobacterium Phormidium valderianum BDU 20041. Bioresour Technol 57:111–116CrossRefGoogle Scholar
  187. 187.
    Taikhao S, Junyapoon S, Incharoensakdi A, Phunpruch S (2013) Factors affecting biohydrogen production by unicellular halotolerant cyanobacterium Aphanothece halophytica. J Appl Phycol 25:575–585CrossRefGoogle Scholar
  188. 188.
    Kothari A, Parameswaran P, Garcia-Pichel F (2014) Powerful fermentative hydrogen evolution of photosynthate in the cyanobacterium Lyngbya aestuarii BL J mediated by a bidirectional hydrogenase. Front Microbiol 5:680PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Feist AM, Herrgard MJ, Thiele I, Reed JL, Palsson BO (2009) Reconstruction of biochemical networks in microorganisms. Nat Rev Microbiol 7:129–143PubMedCrossRefGoogle Scholar
  190. 190.
    Hamilton JJ, Reed JL (2012) Identification of functional differences in metabolic networks using comparative genomics and constraint-based models. PLoS One 7:e34670PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Knoop H, Steuer R (2015) A computational analysis of stoichiometric constraints and trade-offs in cyanobacterial biofuel production. Front Bioeng Biotechnol 3:47PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Segre D, Vitkup D, Church GM (2002) Analysis of optimality in natural and perturbed metabolic networks. Proc Natl Acad Sci U S A 99:15112–15117PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Park JH, Lee KH, Kim TY, Lee SY (2007) Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation. Proc Natl Acad Sci U S A 104:7797–7802PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Hendry JI, Prasannan CB, Joshi A, Dasgupta S, Wangikar PP (2016) Metabolic model of Synechococcus sp. PCC 7002: prediction of flux distribution and network modification for enhanced biofuel production. Bioresour Technol 213:190–197PubMedCrossRefGoogle Scholar
  195. 195.
    Yoshikawa K et al (2015) Construction of a genome-scale metabolic model of arthrospira platensis NIES-39 and metabolic design for cyanobacterial bioproduction. PLoS One 10:e0144430PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Lee KH, Park JH, Kim TY, Kim HU, Lee SY (2007) Systems metabolic engineering of Escherichia coli for L-threonine production. Mol Syst Biol 3:149PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Yoshikawa K, Toya Y, Shimizu H (2017) Metabolic engineering of Synechocystis sp. PCC 6803 for enhanced ethanol production based on flux balance analysis. Bioprocess Biosyst Eng 40:791–796PubMedCrossRefGoogle Scholar
  198. 198.
    Sengupta T, Bhushan M, Wangikar PP (2013) Metabolic modeling for multi-objective optimization of ethanol production in a Synechocystis mutant. Photosynth Res 118:155–165PubMedCrossRefGoogle Scholar
  199. 199.
    Wang X, Xiong X, Sa N, Roje S, Chen S (2016) Metabolic engineering of enhanced glycerol-3-phosphate synthesis to increase lipid production in Synechocystis sp. PCC 6803. Appl Microbiol Biotechnol 100:6091–6101PubMedCrossRefGoogle Scholar
  200. 200.
    Bock A, King PW, Blokesch M, Posewitz MC (2006) Maturation of hydrogenases. Adv Microb Physiol 51:1–71PubMedCrossRefGoogle Scholar
  201. 201.
    Fontecilla-Camps JC, Volbeda A, Cavazza C, Nicolet Y (2007) Structure/function relationships of [NiFe]- and [FeFe]-hydrogenases. Chem Rev 107:4273–4303PubMedCrossRefGoogle Scholar
  202. 202.
    King PW, Posewitz MC, Ghirardi ML, Seibert M (2006) Functional studies of [FeFe] hydrogenase maturation in an Escherichia coli biosynthetic system. J Bacteriol 188:2163–2172PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Weyman PD et al (2011) Heterologous expression of Alteromonas macleodii and Thiocapsa roseopersicina [NiFe] hydrogenases in Synechococcus elongatus. PLoS One 6:e20126PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Asada Y et al (2000) Heterologous expression of clostridial hydrogenase in the cyanobacterium Synechococcus PCC7942. Biochim Biophys Acta 1490:269–278PubMedCrossRefGoogle Scholar
  205. 205.
    Berto P et al (2011) The cyanobacterium Synechocystis sp. PCC 6803 is able to express an active [FeFe]-hydrogenase without additional maturation proteins. Biochem Biophys Res Commun 405:678–683PubMedCrossRefGoogle Scholar
  206. 206.
    Gartner K, Lechno-Yossef S, Cornish AJ, Wolk CP, Hegg EL (2012) Expression of Shewanella oneidensis MR-1 [FeFe]-hydrogenase genes in Anabaena sp. strain PCC 7120. Appl Environ Microbiol 78:8579–8586PubMedPubMedCentralCrossRefGoogle Scholar
  207. 207.
    Armstrong FA (2004) Hydrogenases: active site puzzles and progress. Curr Opin Chem Biol 8:133–140PubMedCrossRefGoogle Scholar
  208. 208.
    Burgdorf T et al (2005) [NiFe]-hydrogenases of Ralstonia eutropha H16: modular enzymes for oxygen-tolerant biological hydrogen oxidation. J Mol Microbiol Biotechnol 10:181–196PubMedCrossRefGoogle Scholar
  209. 209.
    Maness PC, Smolinski S, Dillon AC, Heben MJ, Weaver PF (2002) Characterization of the oxygen tolerance of a hydrogenase linked to a carbon monoxide oxidation pathway in Rubrivivax gelatinosus. Appl Environ Microbiol 68:2633–2636PubMedPubMedCentralCrossRefGoogle Scholar
  210. 210.
    Vargas WA, Weyman PD, Tong Y, Smith HO, Xu Q (2011) [NiFe] hydrogenase from Alteromonas macleodii with unusual stability in the presence of oxygen and high temperature. Appl Environ Microbiol 77:1990–1998PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Maroti G et al (2009) Discovery of [NiFe] hydrogenase genes in metagenomic DNA: cloning and heterologous expression in Thiocapsa roseopersicina. Appl Environ Microbiol 75:5821–5830PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    Cohen J, Kim K, King P, Seibert M, Schulten K (2005) Finding gas diffusion pathways in proteins: application to O2 and H2 transport in CpI [FeFe]-hydrogenase and the role of packing defects. Structure 13:1321–1329PubMedCrossRefGoogle Scholar
  213. 213.
    Liebgott PP et al (2011) Original design of an oxygen-tolerant [NiFe] hydrogenase: major effect of a valine-to-cysteine mutation near the active site. J Am Chem Soc 133:986–997PubMedCrossRefGoogle Scholar
  214. 214.
    Lautier T et al (2011) The quest for a functional substrate access tunnel in FeFe hydrogenase. Faraday Discuss 148:385–407.; discussion 421-341PubMedCrossRefGoogle Scholar
  215. 215.
    Dementin S et al (2009) Introduction of methionines in the gas channel makes [NiFe] hydrogenase aero-tolerant. J Am Chem Soc 131:10156–10164PubMedCrossRefGoogle Scholar
  216. 216.
    Brooke EJ et al (2017) Importance of the active site “Canopy” residues in an O2-tolerant [NiFe]-hydrogenase. Biochemistry 56:132–142PubMedCrossRefGoogle Scholar
  217. 217.
    Huang GF et al (2015) Improved O2-tolerance in variants of a H2-evolving [NiFe]-hydrogenase from Klebsiella oxytoca HP1. FEBS Lett 589:910–918PubMedCrossRefGoogle Scholar
  218. 218.
    Duche O, Elsen S, Cournac L, Colbeau A (2005) Enlarging the gas access channel to the active site renders the regulatory hydrogenase HupUV of Rhodobacter capsulatus O2 sensitive without affecting its transductory activity. FEBS J 272:3899–3908PubMedCrossRefGoogle Scholar
  219. 219.
    Buhrke T, Lenz O, Krauss N, Friedrich B (2005) Oxygen tolerance of the H2-sensing [NiFe] hydrogenase from Ralstonia eutropha H16 is based on limited access of oxygen to the active site. J Biol Chem 280:23791–23796PubMedCrossRefGoogle Scholar
  220. 220.
    Cano M et al (2014) Improved oxygen tolerance of the Synechocystis sp. PCC 6803 bidirectional hydrogenase by site-directed mutagenesis of putative residues of the gas diffusion channel. Int J Hydrog Energy 39:16872–16884CrossRefGoogle Scholar
  221. 221.
    Swartz JR, KOO J (2017) In: USPTO (ed) The Board of Trustees of The Leland Stanford Junior UniversityGoogle Scholar
  222. 222.
    van Thor JJ et al (2000) Salt shock-inducible photosystem I cyclic electron transfer in Synechocystis PCC6803 relies on binding of ferredoxin: NADP+ reductase to the thylakoid membranes via its CpcD phycobilisome-linker homologous N-terminal domain. Biochim Biophys Acta (BBA)-Bioenerg 1457:129–144CrossRefGoogle Scholar
  223. 223.
    Eilenberg H et al (2016) The dual effect of a ferredoxin-hydrogenase fusion protein in vivo: successful divergence of the photosynthetic electron flux towards hydrogen production and elevated oxygen tolerance. Biotechnol Biofuels 9:182PubMedPubMedCentralCrossRefGoogle Scholar
  224. 224.
    Yacoby I et al (2011) Photosynthetic electron partitioning between [FeFe]-hydrogenase and ferredoxin:NADP+-oxidoreductase (FNR) enzymes in vitro. Proc Natl Acad Sci U S A 108:9396–9401PubMedPubMedCentralCrossRefGoogle Scholar
  225. 225.
    Masukawa H, Inoue K, Sakurai H (2007) Effects of disruption of homocitrate synthase genes on Nostoc sp. strain PCC 7120 photobiological hydrogen production and nitrogenase. Appl Environ Microbiol 73:7562–7570PubMedPubMedCentralCrossRefGoogle Scholar
  226. 226.
    Weyman PD, Pratte B, Thiel T (2010) Hydrogen production in nitrogenase mutants in Anabaena variabilis. FEMS Microbiol Lett 304:55–61PubMedCrossRefGoogle Scholar
  227. 227.
    Masukawa H, Inoue K, Sakurai H, Wolk CP, Hausinger RP (2010) Site-directed mutagenesis of the Anabaena sp. strain PCC 7120 nitrogenase active site to increase photobiological hydrogen production. Appl Environ Microbiol 76:6741–6750PubMedPubMedCentralCrossRefGoogle Scholar
  228. 228.
    Masukawa H, Sakurai H, Hausinger RP, Inoue K (2014) Sustained photobiological hydrogen production in the presence of N2 by nitrogenase mutants of the heterocyst-forming cyanobacterium Anabaena. Int J Hydrog Energy 39:19444–19451CrossRefGoogle Scholar
  229. 229.
    Seibert M, Benson DK, Flynn TM (2001). USAGoogle Scholar
  230. 230.
    Katsuda T, Oshima H, Azuma M, Kato J (2006) New detection method for hydrogen gas for screening hydrogen-producing microorganisms using water-soluble Wilkinson's catalyst derivative. J Biosci Bioeng 102:220–226PubMedCrossRefGoogle Scholar
  231. 231.
    Schrader PS, Burrows EH, Ely RL (2008) High-throughput screening assay for biological hydrogen production. Anal Chem 80:4014–4019PubMedCrossRefGoogle Scholar
  232. 232.
    Wecker MSA, Meuser JE, Posewitz MC, Ghirardi ML (2011) Design of a new biosensor for algal H-2 production based on the H-2-sensing system of Rhodobacter capsulatus. Int J Hydrog Energy 36:11229–11237CrossRefGoogle Scholar
  233. 233.
    Wecker MSA, Ghirardi ML (2014) High-throughput biosensor discriminates between different algal H-2-photoproducing strains. Biotechnol Bioeng 111:1332–1340PubMedCrossRefGoogle Scholar
  234. 234.
    Boyer ME, Stapleton JA, Kuchenreuther JM, Wang CW, Swartz JR (2008) Cell-free synthesis and maturation of [FeFe] hydrogenases. Biotechnol Bioeng 99:59–67PubMedCrossRefGoogle Scholar
  235. 235.
    Kuchenreuther JM, Stapleton JA, Swartz JR (2009) Tyrosine, cysteine, and S-adenosyl methionine stimulate in vitro [FeFe] hydrogenase activation. PLoS One 4:e7565PubMedPubMedCentralCrossRefGoogle Scholar
  236. 236.
    Stapleton JA, Swartz JR (2010) Development of an in vitro compartmentalization screen for high-throughput directed evolution of [FeFe] hydrogenases. PLoS One 5:e15275PubMedPubMedCentralCrossRefGoogle Scholar
  237. 237.
    Barahona E, Jimenez-Vicente E, Rubio LM (2016) Hydrogen overproducing nitrogenases obtained by random mutagenesis and high-throughput screening. Sci Rep 6:38291PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Anagha Krishnan
    • 1
  • Xiao Qian
    • 2
  • Gennady Ananyev
    • 2
  • Desmond S. Lun
    • 3
    • 4
    • 5
  • G. Charles Dismukes
    • 2
    • 6
    Email author
  1. 1.Department of BiochemistryUniversity of AlbertaEdmontonCanada
  2. 2.Waksman InstituteRutgers UniversityPiscatawayUSA
  3. 3.Center for Computational and Integrative BiologyRutgers, The State University of New JerseyCamdenUSA
  4. 4.Department of Computer ScienceRutgers, The State University of New JerseyCamdenUSA
  5. 5.Department of Plant BiologyRutgers, The State University of New JerseyNew BrunswickUSA
  6. 6.Department of Chemistry & Chemical BiologyRutgers UniversityPiscatawayUSA

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