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Plant Cell Reports

, Volume 24, Issue 11, pp 629–641 | Cite as

Microalgae as bioreactors

  • Tara L. Walker
  • Saul Purton
  • Douglas K. Becker
  • Chris Collet
Review

Abstract

Microalgae already serve as a major natural source of valuable macromolecules including carotenoids, long-chain polyunsaturated fatty acids and phycocolloids. As photoautotrophs, their simple growth requirements make these primitive plants potentially attractive bioreactor systems for the production of high-value heterologous proteins. The difficulty of producing stable transformants has meant that the field of transgenic microalgae is still in its infancy. Nonetheless, several species can now be routinely transformed and algal biotechnology companies have begun to explore the possibilities of synthesizing recombinant therapeutic proteins in microalgae and the engineering of metabolic pathways to produce increased levels of desirable compounds. In this review, we compare the current commercially viable bioreactor systems, outline recent progress in microalgal biotechnology and transformation, and discuss the potential of microalgae as bioreactors for the production of heterologous proteins.

Keywords

Green Fluorescent Protein Astaxanthin Heterologous Protein Total Soluble Protein Mass Culture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Allnutt FCT, Kyle DJ, Grossman AR, Apt KE (2000) Methods and tools for transformation of eukaryotic algae. United States of America Patent Number 6027900Google Scholar
  2. Apt KE, Behrens PW (1999) Commercial developments in microalgal biotechnology. J Phycol 35:215–226CrossRefGoogle Scholar
  3. Apt KE, Kroth-Pancic PG, Grossman AR (1996) Stable nuclear transformation of the diatom Phaeodactylum tricornutum. Mol Gen Genet 252:572–579CrossRefPubMedGoogle Scholar
  4. Armbrust EV, Berges JA, Bowler C, Green BR, Martinez D, Putnam N, Zhou S, Allen AE, Apt KE, Bechner M, Brzezinski MA, Chaal BK, Chiovitti A, Davis AK, Demarest MS, Detter JC, Glavina T, Goodstein D, Hadi MZ, Hellsten U, Hilldebrand M, Jenkins BD, Jurka J, Kapitonov VV, Kröger N, Lau WWY, Lane TW, Larimer FW, Lippmeier JC, Lucas S, Medina M, Monstant A, Orbornik M, Parker MS, Palenik B, Pazour GJ, Richardson PM, Rynearson TA, Saito MA, Schwartz DC, Thamatakoln K, Valentin K, Vardi A, Wilkerson FP, Rokshar D (2004) The genome of the diatom Thalassiosira pseudonana: ecology, evolution, and metabolism. Science 306:79–86CrossRefPubMedGoogle Scholar
  5. Bateman JM, Purton S (2000) Tools for chloroplast transformation in Chlamydomonas: expression vectors and a new dominant selectable marker. Mol Gen Genet 263:404–410CrossRefPubMedGoogle Scholar
  6. Banicki JJ (2004) An alga a day keeps the doctor away. Engineered algae as a new means to vaccinate fish. Twine Line 26:1–2Google Scholar
  7. Benemann JR (2003) Biofixation of CO2 and greenhouse gas abatement with microalgae—technology roadmap. Final report to the US Department of Energy, National Energy Technology LaboratoryGoogle Scholar
  8. Benemann JR, Oswald WJ (1996) Systems and economic analysis of microalgae ponds for conversion of CO2 to biomass. Final report to the US Department of Energy, Pittsburgh Energy Technology CenterGoogle Scholar
  9. Benfey PN, Ren L, Chua NH (1990) Tissue-specific expression from CaMV 35S enhancer subdomains in early stages of plant development. EMBO J 9:1677–1684PubMedGoogle Scholar
  10. Borisjuk NV, Borisjuk LG, Logendra S, Petersen F, Gleba Y, Raskin I (1999) Production of recombinant proteins in plant root exudates. Nat Biotechnol 17:466–469CrossRefPubMedGoogle Scholar
  11. Borovsky D (2003) Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control. J Exp Biol 206:3869–3875CrossRefPubMedGoogle Scholar
  12. Borowitzka MA (1988) Vitamins and fine chemicals from micro-algae. In: Borowitzka LJ, Borowitzka MA (eds) Micro-algal biotechnology. Cambridge University Press, Cambridge, pp 153–196Google Scholar
  13. Borowitzka MA (1999) Commercial production of microalgae. In: Cohen Z (ed) Chemicals from microalgae. Taylor & Francis, London, pp 313–352Google Scholar
  14. Boynton JE, Gillham NW, Harris EH, Hosler JP, Johnson AM, Jones AR, Randolph-Anderson BL, Robertson D, Klein TM, Shark KB, Sanford JC (1988) Chloroplast transformation in Chlamydomonas with high velocity microprojectiles. Science 240:1534–1538PubMedGoogle Scholar
  15. Brown LE, Sprecher SL, Keller LR (1991) Introduction of exogenous DNA into Chlamydomonas reinhardtii by electroporation. Mol Cell Biol 11:2328–2332PubMedGoogle Scholar
  16. Brown MR (2002) Nutritional value of microalgae for aquaculture. In: Cruz-Suarez LE, Ricque-Marie D, Tapia-Salazar M, Gaxiola-Cortes MG, Simoes N (eds) Avances en nutricion acuicola VI. Memorias del VI SymposiumInternacional de Nutricion Acuicola. 3–6th September, Cancun, MexicoGoogle Scholar
  17. Cabanes-Macheteau M, Fitchette-Laine AC, Loutelie-Bourhis C, Lange C, Vine N, Ma J, Lerouge P, Faye L (1999) N-Glycosylation of a mouse IgG expressed in transgenic tobacco plants. Glycobiology 9:365–372CrossRefPubMedGoogle Scholar
  18. Cannell RJP (1993) Algae as a source of biologically active products. Pest Sci 39:147–153Google Scholar
  19. Cerutti H, Johnson AM, Gillham NW, Boynton JE (1997) A eubacterial gene conferring spectinomycin resistance on Chlamydomonas reinhardtii: integration into the nuclear genome and gene expression. Genetics 145:97–110PubMedGoogle Scholar
  20. Chen Y, Wang Y, Sun Y., Zhang L, Li W (2001) Highly efficient expression of rabbit neutrophil peptide-1 gene in Chlorella ellipsoidea cells. Curr Genet 39:365–370CrossRefPubMedGoogle Scholar
  21. Chow KC, Tung WL (1999) Electrotransformation of Chlorella vulgaris. Plant Cell Rep 18:778–780CrossRefGoogle Scholar
  22. Chu L, Robinson DK (2001) Industrial choices for protein productions by large-scale cell culture. Curr Opin Biotechnol 12:180–187CrossRefPubMedGoogle Scholar
  23. Codd GA (1995) Cyanobacterial toxins: occurrence, properties and biological significance. Wat Sci Technol 32:149–156CrossRefGoogle Scholar
  24. Cohen Z (1999) (ed.) Chemicals from microalgae. Taylor & Francis Ltd., LondonGoogle Scholar
  25. Cramer CL, Weissenborn DL, Oishi KK, Grabau EA, Bennett S, Ponce E, Grabowski GA, Radin DN (1996) Bioproduction of human enzymes in transgenic tobacco. Ann NY Acad Sci 792:62–71PubMedGoogle Scholar
  26. Cramer CL, Boothe JG, Oishi KK (1999) Transgenic plants for therapeutic proteins: linking upstream and downstream strategies. Curr Top Microbiol Immunol 240:95–118PubMedGoogle Scholar
  27. Curtain C (2000) The growth of Australia's algal beta-carotene industry. Australian Biotechnol 10:19–23Google Scholar
  28. Davies JP, Weeks DP, Grossman AR (1992) Expression of the arylsulfatase gene from the beta 2-tubulin promoter in Chlamydomonas reinhardtii. Nucleic Acids Res 20:2959–2965PubMedGoogle Scholar
  29. Dawson HN, Burlingame R, Cannons AC (1997) Stable transformation of Chlorella: Rescue of nitrate reductase-deficient mutants with the nitrate reductase gene. Curr Microbio 35:356–362CrossRefGoogle Scholar
  30. Debuchy R, Purton S, Rochaix JD (1989) The argininosuccinate lyase gene of Chlamydomonas reinhardtii: an important tool for nuclear transformation and for correlating the genetic and molecular maps of the ARG7 locus. EMBO J 8:2803–2809PubMedGoogle Scholar
  31. De Cosa B, Moar W, Lee SB, Miller M, Daniell H (2001) Over expression of the Bt cry2Aa2 operon in chloroplasts leads to formation of insecticidal crystals. Nat Biotechnol 19:71–74CrossRefPubMedGoogle Scholar
  32. Doetsch NA, Favreau MR, Kuscuoglu N, Thompson MD, Hallick RB (2001) Chloroplast transformation in Euglena gracilis: splicing of a group III twintron transcribed from a transgenic psbK operon. Curr Genet 39:49–60CrossRefPubMedGoogle Scholar
  33. Dunahay TG (1993) Transformation of Chlamydomonas reinhardtii with silicon carbide whiskers. Biotechniques 15:452–460PubMedGoogle Scholar
  34. Dunahay TG, Jarvis EE, Roessler PG (1995) Genetic transformation of the diatoms Cyclotella cryptica and Navicula saprophila. J Phycol 31:1004–1012CrossRefGoogle Scholar
  35. Echelard Y (1996) Recombinant protein production in transgenic animals. Curr Opin Biotechnol 7:536–540CrossRefPubMedGoogle Scholar
  36. El-Sheekh MM (1999) Stable transformation of the intact cells of Chlorella kessleri with high velocity microprojectiles. Biologia Plantarum 42:209–216CrossRefGoogle Scholar
  37. Falciatore A, Bowler C (2002) Revealing the molecular secrets of marine diatoms. Annu Rev Plant Biol 53:109–130CrossRefPubMedGoogle Scholar
  38. Fernandez E, Schnell R, Ranum LP, Hussey SC, Silflow CD, Lefebvre PA (1989) Isolation and characterization of the nitrate reductase structural gene of Chlamydomonas reinhardtii. Proc Natl Acad Sci USA 86:6449–6453PubMedGoogle Scholar
  39. Fischer R, Emans N (2000) Molecular farming of pharmaceutical proteins. Transgenic Res 9:279–299CrossRefPubMedGoogle Scholar
  40. Fischer R, Liao YC, Hoffmann K, Schillberg S, Emans N (1999) Molecular farming of recombinant antibodies in plants. Biol Chem 380:825–839CrossRefPubMedGoogle Scholar
  41. Franklin SE, Mayfield SP (2004) Prospects for molecular farming in the green alga Chlamydomonas. Curr Opin Plant Biol 7:159–165CrossRefPubMedGoogle Scholar
  42. Franklin S, Ngo B, Efuet E, Mayfield SP (2002) Development of a GFP reporter gene for Chlamydomonas reinhardtii chloroplast. Plant J 30:733–744CrossRefPubMedGoogle Scholar
  43. Fuhrmann M (2002) Expanding the molecular toolkit for Chlamydomonas reinhardtii—from history to new frontiers. Protist 153:357–364CrossRefPubMedGoogle Scholar
  44. Fuhrmann M, Hausherr A, Ferbitz L, Schödl T, Heitzer M, Hegemann P (2004) Monitoring dynamic expression of nuclear genes in Chlamydomonas reinhardtii by using a synthetic luciferase reporter gene. Plant Mol Biol 55:869–881PubMedGoogle Scholar
  45. Fuhrmann M, Oertel W, Hegemann P (1999) A synthetic gene coding for the green fluorescent protein (GFP) is a versatile reporter in Chlamydomonas reinhardtii. Plant J 19:353–361CrossRefPubMedGoogle Scholar
  46. Ganz PR (1996) Expression of human blood proteins in transgenic plants: the cytokine GM-CSF as a model protein. In: Owen MRL, Pen J (eds) Transgenic plants: a production system for industrial and pharmaceutical proteins. Wiley, London, pp 281–297Google Scholar
  47. Garcia-Casado G, Sanchez-Monge R, Chrispeels MJ, Armentia A, Salcedo G, Gomez L (1996) Role of complex asparagine-linked glycans in the allergenicity of plant glycoproteins. Glycobiology 6:471–477PubMedGoogle Scholar
  48. Geng D, Wang Y, Wang P, Li W, Sun Y (2003) Stable expression of hepatitis B surface antigen in Dunaliella salina (Chlorophyta). J App Phycol 15:451–456CrossRefGoogle Scholar
  49. Giddings G, Allison G, Brooks D, Carter A (2000) Transgenic plants as factories for biopharmaceuticals. Nat Biotechnol 18:1151–1155CrossRefPubMedGoogle Scholar
  50. Goldschmidt-Clermont M (1991) Transgenic expression of aminoglycoside adenine transferase in the chloroplast: a selectable marker of site-directed transformation of Chlamydomonas. Nucleic Acids Res 19:4083–4089PubMedGoogle Scholar
  51. Gomord V, Denmat LA, Fitchette-Laine AC, Satiat-Jeunemaitre B, Hawes C, Faye L (1997) The C-terminal HDEL sequence is sufficient for retention of secretory proteins in the endoplasmic reticulum (ER) but promotes vacuolar targeting of proteins that escape the ER. Plant J 11:101–103CrossRefGoogle Scholar
  52. Grinnell BW, Walls JD, Gerlitz B (1991) Glycosylation of human protein C affects its secretion, processing, functional activities, and activation by thrombin. J Biol Chem 266:9778–9785PubMedGoogle Scholar
  53. Grossman AR, Harris EE, Hauser C, Lefebvre PA, Martinez D, Rokhsar D, Shrager J, Silflow CD, Stern D, Vallon O, Zhang Z (2003) Chlamydomonas reinhardtii at the crossroads of genomics. Eukaryotic Cell 2:1137–1150CrossRefPubMedGoogle Scholar
  54. Hawkins RL, Nakamura M (1999) Expression of human growth hormone by the eukaryotic alga, Chlorella. Curr Microbiol 38:335–341PubMedGoogle Scholar
  55. He Q (2003) Microalgae as platforms for recombinant proteins. In: Richmond A (ed) Handbook of microalgal culture: biotechnology and applied phycology. Blackwell Publishing, Oxford, UK, pp 471–484Google Scholar
  56. Herbers K, Sonnewald U (1999) Production of new/modified proteins in transgenic plants. Curr Opin Biotechnol 10:163–168CrossRefPubMedGoogle Scholar
  57. Hiatt AC, Cafferkey R, Bowdish K (1989) Production of antibodies in transgenic plants. Nature 342:76–78CrossRefPubMedGoogle Scholar
  58. Ishikura K, Tataoka Y, Kata K, Sekine M, Yoshida K, Shinmyo A (1999) Expression of a foreign gene in Chlamydomonas reinhardtii chloroplast. J Biosci Bioeng 87:307–334CrossRefPubMedGoogle Scholar
  59. Janne J, Alhonen L, Hyttinen JM, Peura T, Tolvanen M, Korhonen VP (1998) Transgenic bioreactors. Biotechnol Annu Rev 4:55–74PubMedGoogle Scholar
  60. Jarvis EE, Brown LM (1991) Transient expression of firefly luciferase in protoplasts of the green alga Chlorella ellipsoidea. Curr Genet 19:317–321CrossRefGoogle Scholar
  61. Jefferis R, Lund J (1997) Glycosylation of antibody molecules: structural and functional significance. Chem Immun Antibody Eng 65:111–128Google Scholar
  62. Kang M, Han JG, Liu PF, Ye Y, Tien P (2000) The regulation activity of Chlorella virus gene 5′ upstream sequence in Escherichia coli and eucaryotic algae. Sheng Wu Gong Cheng Xue Bao 16:443–446PubMedGoogle Scholar
  63. Kelley BD (2001) Biochemical engineering: bioprocessing of therapeutic proteins. Curr Opin Biotechnol 12:173–174CrossRefPubMedGoogle Scholar
  64. Kim D-H, Kim YT, Cho JJ, Bae J-H, Hur S-B, Hwang I, Choi T-J (2002) Stable integration and functional expression of flounder growth hormone gene in transformed microalga, Chlorella ellipsoidea. Marine Biotechnol 4:63–73CrossRefGoogle Scholar
  65. Kindle KL, Schnell RA, Fernandez E, Lefebvre PA (1989) Stable nuclear transformation of Chlamydomonas using the Chlamydomonas gene for nitrate reductase. J Cell Biol 109:2589–2601CrossRefPubMedGoogle Scholar
  66. Kindle KL (1990) High-frequency nuclear transformation of Chlamydomonas reinhardtii. Proc Natl Acad Sci USA 87:1228–1232PubMedGoogle Scholar
  67. Komine Y, Kikis E, Schuster G, Stern D (2002) Evidence for in vivo modulation of chloroplast RNA stability by 3′-UTR homopolymeric tails in Chlamydomonas reinhardtii. Proc Natl Acad Sci USA 99:4085–4090CrossRefPubMedGoogle Scholar
  68. Kovar JL, Zhang J, Funke RP, Weeks DP (2002) Molecular analysis of the acetolactate synthase gene of Chlamydomonas reinhardtii and development of a genetically engineered gene as a dominant selectable marker for genetic transformation. Plant J 29:109–117CrossRefPubMedGoogle Scholar
  69. Kumar SV, Misquitta RW, Reddy VS, Rao BJ, Rajam MV (2004) Genetic transformation of the green alga—Chlamydomonas reinhardtii by Agrobacterium tumefaciens. Plant Science 166:731–738CrossRefGoogle Scholar
  70. Lapidot M, Raveh D, Sivan A, Arad SM, Shapira M (2002) Stable chloroplast transformation of the unicellular red alga Porphyridium species. Plant Physiol 129:7–12CrossRefPubMedGoogle Scholar
  71. Larrick JW, Thomas DW (2001) Producing proteins in transgenic plants and animals. Curr Opin Biotechnol 12:411–418CrossRefPubMedGoogle Scholar
  72. Lee Y-K (2001) Microalgal mass culture systems and methods: Their limitation and potential. J Appl Phycol 13:307–315CrossRefGoogle Scholar
  73. Lin Cereghino GPL, Cregg JM (1999) Applications of yeast in biotechnology: protein production and genetic analysis. Curr Opin Biotechnol 10:422–427CrossRefPubMedGoogle Scholar
  74. Lorenz RT, Cysewski GR (2000) Commercial potential for Haematococcus microalgae as a natural source of astaxanthin. Trends Biotechnol 18:160–167CrossRefPubMedGoogle Scholar
  75. Lumbreras V, Purton S (1998) Recent advances in Chlamydomonas transgenics. Protist 149:23–27CrossRefGoogle Scholar
  76. Lumbreras V, Stevens DR, Purton S (1998) Efficient foreign gene expression in Chlamydomonas reinhardtii mediated by an endogenous intron. Plant J 14:441–147CrossRefGoogle Scholar
  77. Ma JKC, Hiatt A (1996) Expressing antibodies in plants for immunotherapy. In: Owen MRL, Pen P (eds) Transgenic plants: a production system for industrial and pharmaceutical proteins. Wiley, London, pp 229–243Google Scholar
  78. Ma JKC, Hikmat BY, Wycoff K, Vine ND, Chargelegue D, Yu L, Hein MB, Lehner T (1998) Characterisation of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med 4:601–606CrossRefPubMedGoogle Scholar
  79. Mason HS, Lam DM, Arntzen CJ (1992) Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci USA 89:11745–11749PubMedGoogle Scholar
  80. Mason HS, Arntzen CJ (1995) Transgenic plants as vaccine production systems. Trends Biotechnol 13:388–392CrossRefPubMedGoogle Scholar
  81. Masuda T, Tanaka A, Melis A (2003) Chlorophyll antenna size adjustments by irradiance in Dunaliella salina involve coordinate regulation of chlorophyll a oxygenase (CAO) and Lhcb gene expression. Plant Mol Biol 51:757–771CrossRefPubMedGoogle Scholar
  82. Matsuzaki M, Misumi O, Shin-I T, Maruyama S, Takahara M, Miyagishima S, Mori T, Nishida K, Yagisawa F, Nishida K, Yoshida Y, Nishimura Y, Nakao S, Kobayashi T, Momoyama Y, Higashiyama T, Minoda A, Sano M, Nomoto H, Oishi K, Hayashi H, Ohta F, Nishizaka S, Haga S, Miura S, Morishita T, Kabeya Y, Terasawa K, Suzuki Y, Ishii Y, Asakawa S, Takano H, Ohta N, Kuroiwa H, Tanaka K, Shimizu N, Sugano S, Sato N, Nozaki H, Ogasawara N, Kohara Y, Kuroiwa T (2004) Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature 428:653–657CrossRefPubMedGoogle Scholar
  83. Mayfield SP, Franklin SE, Lerner RA (2003) Expression and assembly of a fully active antibody in algae. Proc Natl Acad Sci USA 100:438–442CrossRefPubMedGoogle Scholar
  84. Mayfield SP, Schultz J (2004) Development of a luciferase reporter gene, luxCt, for Chlamydomonas reinhardtii chloroplast. Plant J 37:449–458CrossRefPubMedGoogle Scholar
  85. Melis A, Neidhardt J, Benemann JR (1999) Dunaliella salina (Chlorophyta) with small chlorophyll antenna sizes exhibit higher photosynthetic productivities and photon use efficiencies than normally pigmented cells. J Appl Phycol 10:515–525CrossRefGoogle Scholar
  86. Melis A, Zhang L, Forestier M, Ghiradi ML, Seibert M (2000) Sustained hydrogen gas production upon reversible inactivation of oxygen evolution in the green alga Chlamydomonas reinhardtii. Plant Physiol 122:127–135CrossRefPubMedGoogle Scholar
  87. Miele L (1997) Plants as bioreactors for biopharmaceuticals: regulatory considerations. Trends Biotechnol 15:45–50CrossRefPubMedGoogle Scholar
  88. Minoda A, Sakagami R, Yagisawa F, Kuroiwa T, Tanaka K (2004) Improvement of culture conditions and evidence for nuclear transformation by homologous recombination in a red alga, Cyanidioschyzon merolae 10D. Plant Cell Physiol 45:667–671CrossRefPubMedGoogle Scholar
  89. Mitra A, Higgins DW (1994) The Chlorella virus adenine methyltransferase gene promoter is a strong promoter in plants. Plant Mol Biol 26:85–93CrossRefPubMedGoogle Scholar
  90. Moore RE (1996) Cyclic peptides and depsipeptides from cyanobacteria: a review. J Ind Microbiol 16:134–143CrossRefPubMedGoogle Scholar
  91. Mor TS, Sternfeld M, Soreq H, Arntzen CJ, Mason HS (2001) Expression of recombinant human acetylcholinesterase in transgenic tomato plants. Biotechnol Bioeng 75:259–266CrossRefPubMedGoogle Scholar
  92. Nakajima Y, Ueda R (2000) The effect of reducing light-harvesting pigment on marine microalgal productivity. J Appl Phycol 12:285–290CrossRefGoogle Scholar
  93. Nelson JA, Savereide PB, Lefebvre PA (1994) The CRY1 gene in Chlamydomonas reinhardtii: structure and use as a dominant selectable marker for nuclear transformation. Mol Cell Biol 14:4011–4019PubMedGoogle Scholar
  94. Ördög V, Stirk WA, Lenobel R, Bancírová M, Strnad M, van Staden J, Szigeti J, Németh L (2004) Screening microalgae for some potentially useful agricultural and pharmaceutical secondary metabolites. J Appl Phycol 16:309–314CrossRefGoogle Scholar
  95. Polle JEW, Benemann JR, Tanaka A, Melis A (2000) Photosynthetic apparatus organisation and function in the wild type and a chlorophyll b-less mutant of Chlamydomonas reinhardtii. Dependence on carbon source. Planta 211:335–344CrossRefPubMedGoogle Scholar
  96. Ramirez N, Ayala M, Lorenzo D, Palenzuela D, Herrera L, Doreste V, Perez M, Gavilond JV, Oramas P (2002) Expression of a single-chain Fv antibody fragment specific for the hepatitis B surface antigen in transgenic tobacco plants. Transgenic Res 11:61–64CrossRefPubMedGoogle Scholar
  97. Randolph-Anderson BL, Boynton JE, Gillham NW, Harris EH, Johnson AM, Dorthu MP, Matagne RF (1993) Further characterization of the respiratory deficient dum-1 mutation of Chlamydomonas reinhardtii and its use as a recipient for mitochondrial transformation. Mol Gen Genet 236:235–244CrossRefPubMedGoogle Scholar
  98. Randolph-Anderson BL, Sato R, Johnson AM, Harris EH, Hauser CR, Oeda K, Ishige F, Nishio S, Gillham NW, Boynton JE (1998) Isolation and characterization of a mutant protoporphyrinogen oxidase gene from Chlamydomonas reinhardtii conferring resistance to porphyric herbicides. Plant Mol Biol 38:839–859CrossRefPubMedGoogle Scholar
  99. Rayon C, Cabanes-Macheteau M, Loutelie-Bourhis C, Saliot-Maire I, Lemoine J, Reiter WD, Lerouge P, Faye L (1999) Characterisation of M-glycans from Arabidopsis thaliana. Application to a fucose-deficient mutant of Arabidopsis. Science 261:1032–1035Google Scholar
  100. Reed ML, Wilson SK, Sutton CA, Hanson MR (2001) High-level expression of a synthetic red-shifted GFP coding region incorporated into transgenic chloroplasts. Plant J 27:257–265CrossRefPubMedGoogle Scholar
  101. Rhame LG, Tan MW, Le L, Wong SM, Tompkins RG, Calderwood SB, Ausubel FM (1997) Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. Proc Natl Acad Sci USA 94:13245–13250CrossRefPubMedGoogle Scholar
  102. Ruiz-Binder NE, Geimer S, Melkonian M (2002) In vivo localisation of centrin in the green alga Chlamydomonas reinhardtii. Cell Motil Cytoskeleton 52:43–55CrossRefPubMedGoogle Scholar
  103. Schiedlmeier B, Schmitt R, Muller W, Kirk MM, Gruber H, Mages W, Kirk DL (1994) Nuclear transformation of Volvox carteri. Proc Natl Acad Sci USA 91:5080–5084PubMedGoogle Scholar
  104. Schutt C, Furll B, Stelter F, Jack RS, Witt S (1997) CHO transfectants produce large amounts of recombinant protein in suspension culture. J Immunol Methods 204:99–102CrossRefPubMedGoogle Scholar
  105. Schroda M, Blocker D, Beck CF (2000) The HSP70A promoter as a tool for the improved expression of transgenes in Chlamydomonas. Plant J 21:121–131CrossRefPubMedGoogle Scholar
  106. Schwartz RE, Hirsch CF, Sesin DF, Flor JE, Chartrain M, Fromtling RE, Harris GH, Salvatore MJ, Liesch JM, Yudin K (1990) Pharmaceuticals from cultured algae. J Ind Microbiol 5:113–124CrossRefGoogle Scholar
  107. Scott MR, Will R, Ironside J, Nguyen HO, Tremblay P, DeArmond SJ, Prusiner SB (1999) Compelling transgenic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci USA 96:15137–15142CrossRefPubMedGoogle Scholar
  108. Shimizu Y (1996) Microalgal metabolites: a new perspective. Ann Rev Microbiol 50:431–465CrossRefGoogle Scholar
  109. Shimogawara K, Fujiwara S, Grossman A, Usuda H (1998) High-efficiency transformation of Chlamydomonas reinhardtii by electroporation. Genetics 148:1821–1828PubMedGoogle Scholar
  110. Sijmons PC, Dekker BMM, Schrammeijer B, Verwoerd TC, van den Elzen PJM, Hoekema A (1990) Production of correctly processed human serum albumin in transgenic plants. Bio/Technology 8:217–221CrossRefPubMedGoogle Scholar
  111. Siripornadulsil S, Traina S, Verma DPS, Sayre RT (2002) Molecular mechanisms of proline-mediated tolerance to toxic heavy metals in transgenic microalgae. Plant Cell 14:2837–2847CrossRefPubMedGoogle Scholar
  112. Sizova I, Fuhrmann M, Hegemann P (2001) A Streptomyces rimosus aphVIII gene coding for a new type phosphotransferase provides stable antibiotic resistance to Chlamydomonas reinhardtii. Gene 277:221–229CrossRefPubMedGoogle Scholar
  113. Staub JM, Garcia B, Graves J, Hajdukiewicz PTJ, Hunter P, Nehra N, Paradakar V, Schlittler M, Carroll JA, Spatola L, Ward D, Ye G, Russell DA (2000) High-yield production of a human therapeutic protein in tobacco chloroplasts. Nat Biotechnol 18:333–338CrossRefPubMedGoogle Scholar
  114. Stevens DR, Rochaix JD, Purton S (1996) The bacterial phleomycin resistance gene ble as a dominant selectable marker in Chlamydomonas. Mol Gen Genet 251:23–30CrossRefPubMedGoogle Scholar
  115. Stevens DR, Purton S (1997) Genetic engineering of eukaryotic algae: progress and prospects. J Phycol 33:713–722CrossRefGoogle Scholar
  116. Streatfield SJ, Lane JR, Brooks CA, Barker DK, Poage ML, Mayor JM, Lamphear BJ, Drees CF, Jilka JM, Hood EE, Howard JA (2003) Corn as a production system for human and animal vaccines. Vaccine 21:812–815CrossRefPubMedGoogle Scholar
  117. Sun M, Qian K, Su N, Chang H, Liu J, Chen G (2003) Foot-and-mouth disease virus VP1 protein fused with cholera toxin B subunit expressed in Chlamydomonas reinhardtii chloroplast. Biotechnol Lett 25:1087–1092CrossRefPubMedGoogle Scholar
  118. Swartz JR (2001) Advances in Escherichia coli production of therapeutic proteins. Curr Opin Biotechnol 12:195–201CrossRefPubMedGoogle Scholar
  119. ten Lohuis MR, Miller DJ (1998) Genetic transformation of dinoflagellates (Amphidinium and Symbiodinium): expression of GUS in microalgae using heterologous promoter constructs. Plant J 13:427–435CrossRefGoogle Scholar
  120. Teng C, Qin S, Liu J, Yu D, Liang C, Tseng C (2002) Transient expression of lacZ in bombarded unicellular green alga Haematococcus pluvialis. J Appl Phycol 14:495–500CrossRefGoogle Scholar
  121. Tregoning JS, Nixon P, Kuroda H, Svab Z, Clare S, Bowe F, Fairweather N, Ytterberg J, van Wijk KJ, Dougan G, Maliga P (2003) Expression of tetanus toxin Fragment C in tobacco chloroplasts. Nucleic Acids Res 31:1174–1179CrossRefPubMedGoogle Scholar
  122. von Schaewen A, Sturm A, O'Neill J, Chrispeels MJ (1993) Isolation of a mutant Arabidopsis plant that lacks N-acetylglucosaminyltransferase I is unable to synthesise Golgi-modified complex N-linked glycans. Plant Physiol 102:1109–1118CrossRefPubMedGoogle Scholar
  123. Wall RJ, Hawk HW, Nel N (1992) Making transgenic livestock: Genetic engineering on a large scale. J Cell Biochem 49:113–120CrossRefPubMedGoogle Scholar
  124. Wee EQ, Sherrier DJ, Prime TA, Dupree P (1998) Targeting of active sialyltransferase to the plant Golgi apparatus. Plant Cell 10:1759–1768CrossRefPubMedGoogle Scholar
  125. Wenderoth I, von Schaewen A (2000) Isolation and characterisation of plant N-acetylglucosaminyltransferase I (GnTI) cDNA sequences. Functional analyses in the Arabidopsis cgl mutant and in antisense plants. Plant Physiol 123:1097–1108CrossRefPubMedGoogle Scholar
  126. Zaslavskaia LA, Lippmeier JC, Kroth PG, Grossman AR, Apt KE (2000) Transformation of the diatom Phaeodactylum tricornutum (Bacillariophyceae) with a variety of selectable marker and reporter genes. J Pycol 36:379–386Google Scholar
  127. Zaslavskaia LA, Lippmeier JC, Shih C, Ehrhardt D, Grossman AR, Apt KE (2001) Trophic conversion of an obligate photoautotrophic organism through metabolic engineering. Science 292:2073–2075PubMedGoogle Scholar
  128. Zhang L, Happe T, Melis A (2002) Biochemical and morphological characterisation of sulphur-deprived and H2-producing Chlamydomonas reinhardtii (green alga). Planta 214:552–561CrossRefPubMedGoogle Scholar

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© Springer-Verlag 2005

Authors and Affiliations

  • Tara L. Walker
    • 1
  • Saul Purton
    • 2
  • Douglas K. Becker
    • 1
  • Chris Collet
    • 1
  1. 1.Cluster for Molecular Biotechnology, Science Research Centre and CRC for DiagnosticsQueensland University of TechnologyBrisbaneAustralia
  2. 2.Department of BiologyUniversity College LondonLondonUnited Kingdom

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