Establishing Chlamydomonas reinhardtii as an industrial biotechnology host

Plant Journal

Volumn 82, Issue 3, 2015, Pages 532-546

  Scaife, Mark A ^a   Nguyen, Ginnie T D T ^a   Rico, Juan ^a   Lambert, Devinn ^a   Helliwell, Katherine E ^a   Smith, Alison G ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Chlamydomonas reinhardtii; industrial biotechnology; metabolic engineering; rational design; synthetic biology; transgene expression

Indexed keywords

ALGAE; BIOSYNTHESIS; BIOTECHNOLOGY; FOSSIL FUELS; METABOLISM; MICROORGANISMS;

CHLAMYDOMONAS REINHARDTII; INDUSTRIAL BIOTECHNOLOGY; RATIONAL DESIGN; SYNTHETIC BIOLOGY; TRANSGENE EXPRESSION;

METABOLIC ENGINEERING;

CHLAMYDOMONAS REINHARDTII; EUKARYOTA;

BIOTECHNOLOGY; CHLAMYDOMONAS REINHARDTII; GENETICS; METABOLIC ENGINEERING; METABOLISM; PROCEDURES; SYNTHETIC BIOLOGY;

BIOTECHNOLOGY; CHLAMYDOMONAS REINHARDTII; METABOLIC ENGINEERING; SYNTHETIC BIOLOGY;

EID: 84929045412     PISSN: 09607412     EISSN: 1365313X     Source Type: Journal    
DOI: 10.1111/tpj.12781     Document Type: Article

References (147)

1. Allmer, J., Naumann, B., Markert, C., Zhang, M., and, Hippler, M., (2006) Mass spectrometric genomic data mining: novel insights into bioenergetic pathways in Chlamydomonas reinhardtii. Proteomics, 6, 6207-6220.
2. Annaluru, N., Muller, H., Mitchell, L.A., et al.,. (2014) Total synthesis of a functional designer eukaryotic chromosome. Science, 344, 55-58.
3. Anthony, J.R., Anthony, L.C., Nowroozi, F., Kwon, G., Newman, J.D., and, Keasling, J.D., (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab. Eng. 11, 13-19.
4. Baltz, A., Dang, K.-V., Beyly, A., Auroy, P., Richaud, P., Cournac, L., and, Peltier, G., (2014) Plastidial expression of type II NAD(P)H dehydrogenase increases the reducing state of plastoquinones and hydrogen photoproduction rate by the indirect pathway in Chlamydomonas reinhardtii. Plant Physiol. 165, 1344-1352.
5. Barnes, D., Franklin, S., Schultz, J., Henry, R., Brown, E., Coragliotti, A., and, Mayfield, S.P., (2005) Contribution of 5'- and 3'-untranslated regions of plastid mRNAs to the expression of Chlamydomonas reinhardtii chloroplast genes. Mol. Genet. Genomics, 274, 625-636.
6. Bateman, J.M., and, Purton, S., (2000) Tools for chloroplast transformation in Chlamydomonas: expression vectors and a new dominant selectable marker. Mol. Gen. Genet. 263, 404-410.
7. Bellou, S., Baeshen, M.N., Elazzazy, A.M., Aggeli, D., Sayegh, F., and, Aggelis, G., (2014) Microalgal lipids biochemistry and biotechnological perspectives. Biotechnol. Adv. 32, 1476-1493.
8. Berla, B.M., Saha, R., Immethun, C.M., Maranas, C.D., Moon, T.S., and, Pakrasi, H.B., (2013) Synthetic biology of cyanobacteria: unique challenges and opportunities. Front. Microbiol. 4, 246.
9. Berthold, P., Schmitt, R., and, Mages, W., (2002) An Engineered Streptomyces hygroscopicus aph 7" Gene Mediates Dominant Resistance against Hygromycin B in Chlamydomonas reinhardtii. Protist, 153, 401-412.
10. Blaby, I.K., Blaby-Haas, C.E., Tourasse, N., et al.,. (2014) The Chlamydomonas genome project: a decade on. Trends Plant Sci. 19, 672-680.
11. Blowers, A.D., Bogorad, L., Shark, K.B., and, Sanford, J.C., (1989) Studies on Chlamydomonas chloroplast transformation: foreign DNA can be stably maintained in the chromosome. Plant Cell, 1, 123-132.
12. Boyle, N., and, Morgan, J., (2009) Flux balance analysis of primary metabolism in Chlamydomonas reinhardtii. BMC Syst. Biol. 3, 4.
13. Boynton, J., Gillham, N., Harris, E., et al.,. (1988) Chloroplast transformation in Chlamydomonas with high velocity microprojectiles. Science, 240, 1534-1538.
14. Buchholz, K., and, Collins, J., (2013) The roots-a short history of industrial microbiology and biotechnology. Appl. Microbiol. Biotechnol. 97, 3747-3762.
15. Cameron, D.E., Bashor, C.J., and, Collins, J.J., (2014) A brief history of synthetic biology. Nat. Rev. Microbiol. 12, 381-390.
16. Casas-Mollano, J.A., Rohr, J., Kim, E.-J., Balassa, E., van Dijk, K., and, Cerutti, H., (2008) Diversification of the core RNA interference machinery in Chlamydomonas reinhardtii and the role of DCL1 in transposon silencing. Genetics, 179, 69-81.
17. Cazzaniga, S., Dall'Osto, L., Szaub, J., Scibilia, L., Ballottari, M., Purton, S., and, Bassi, R., (2014) Domestication of the green alga Chlorella sorokiniana: reduction of antenna size improves light-use efficiency in a photobioreactor. Biotechnol. Biofuel. 157, 7.
18. Chang, R.L., Ghamsari, L., Manichaikul, A., et al.,. (2011) Metabolic network reconstruction of Chlamydomonas offers insight into light-driven algal metabolism. Mol. Syst. Biol. 7, 518.
19. Chauton, M.S., Reitan, K.I., Norsker, N.H., Tveterås, R., and, Kleivdal, H.T., (2015) A techno-economic analysis of industrial production of marine microalgae as a source of EPA and DHA-rich raw material for aquafeed: research challenges and possibilities. Aquaculture 436, 95-103.
20. Chen, Z., and, Zeng, A.-P., (2013) Protein design in systems metabolic engineering for industrial strain development. Biotechnol. J. 8, 523-533.
21. Chisti, Y., (2007) Biodiesel from microalgae. Biotechnol. Adv. 25, 294-306.
22. Christian, N., May, P., Kempa, S., Handorf, T., and, Ebenhöh, O., (2009) An integrative approach towards completing genome-scale metabolic networks. Mol. Biosyst. 5, 1889-1903.
23. Cogne, G., Rügen, M., Bockmayr, A., Titica, M., Dussap, C.G., Cornet, J.F., and, Legrand, J., (2011) A model-based method for investigating bioenergetic processes in autotrophically growing eukaryotic microalgae: application to the green algae Chlamydomonas reinhardtii. Biotechnol. Prog. 27, 631-640.
24. Croft, M.T., Moulin, M., Webb, M.E., and, Smith, A.G., (2007) Thiamine biosynthesis in algae is regulated by riboswitches. Proc. Natl Acad. Sci. USA, 104, 20770-20775.
25. Dahl, R.H., Zhang, F., Alonso-Gutierrez, J., et al.,. (2013) Engineering dynamic pathway regulation using stress-response promoters. Nat. Biotechnol. 31, 1039-1046.
26. Dal'Molin, C.G., Quek, L.E., Palfreyman, R.W., and, Nielsen, L.K., (2011) AlgaGEM-a genome-scale metabolic reconstruction of algae based on the Chlamydomonas reinhardtii genome. BMC Genom. 12 (Suppl. 4), S5.
27. Davarpanah, S.J., Jung, S.H., Kim, Y.J., Park, Y.-I., Min, S.R., Liu, J.R., and, Jeong, W.J., (2009) Stable plastid transformation in Nicotiana benthamiana. J. Plant Biol. 52, 244-250.
28. Davey, M.P., Horst, I., Duong, G.-H., Tomsett, E.V., Litvinenko, A.C.P., Howe, C.J., and, Smith, A.G., (2014) Triacylglyceride production and autophagous responses in Chlamydomonas reinhardtii depend on resource allocation and carbon source. Eukaryot. Cell, 13, 392-400.
29. Davies, J.P., Weeks, D.P., and, Grossman, A.R., (1992) Expression of the arylsulfatase gene from the f32-tubulin promoter in Chlamydomonas reinhardtii. Nucleic Acids Res., 20, 2959-2965.
30. Day, A., and, Goldschmidt-Clermont, M., (2011) The chloroplast transformation toolbox: selectable markers and marker removal. Plant Biotechnol. J. 9, 540-553.
31. Debuchy, R., Purton, S., and, Rochaix, J.D., (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, 2803-2809.
32. Dorrell, R.G., and, Smith, A.G., (2011) Do red and green make brown?: perspectives on plastid acquisitions within chromalveolates. Eukaryot. Cell, 10, 856-868.
33. Dujon, B., (1998) European Functional Analysis Network (EUROFAN) and the functional analysis of the Saccharomyces cerevisiae genome. Electrophoresis, 19, 617-624.
34. Duvick, J., Fu, A., Muppirala, U., Sabharwal, M., Wilkerson, M.D., Lawrence, C.J., Lushbough, C., and, Brendel, V., (2008) PlantGDB: a resource for comparative plant genomics. Nucleic Acids Res. 36, D959-D965.
35. Eichler-Stahlberg, A., Weisheit, W., Ruecker, O., and, Heitzer, M., (2009) Strategies to facilitate transgene expression in Chlamydomonas reinhardtii. Planta, 229, 873-883.
36. 2-concentrating mechanism regulator CIA5/CCM1. Plant Cell, 24, 1876-1893.
37. Fei, X., and, Deng, X., (2007) A novel Fe deficiency-responsive element (FeRE) regulates the expression of atx1 in Chlamydomonas reinhardtii. Plant Cell Physiol. 48, 1496-1503.
38. Fischer, N., and, Rochaix, J.D., (2001) The flanking regions of PsaD drive efficient gene expression in the nucleus of the green alga Chlamydomonas reinhardtii. Mol. Genet. Genomics, 265, 888-894.
39. Fischer, N., Stampacchia, O., Redding, K., and, Rochaix, J.-D., (1996) Selectable marker recycling in the chloroplast. Mol. Gen. Genet. 251, 373-380.
40. Franklin, S., Ngo, B., Efuet, E., Mayfield, S.P., and, May, S.P., (2002) Development of a GFP reporter gene for Chlamydomonas reinhardtii chloroplast. Plant J. 30, 733-744.
41. Fuhrmann, M., Oertel, W., and, Hegemann, P., (1999) A synthetic gene coding for the green fluorescent protein (GFP) is a versatile reporter in Chlamydomonas reinhardtii. Plant J. 19, 353-361.
42. Gao, H., Wright, D.A., Li, T., Wang, Y., Horken, K., Weeks, D.P., Yang, B., and, Spalding, M.H., (2014) TALE activation of endogenous genes in Chlamydomonas reinhardtii. Algal Res. 5, 52-60.
43. Goel, A., Wortel, M.T., Molenaar, D., and, Teusink, B., (2012) Metabolic shifts: a fitness perspective for microbial cell factories. Biotechnol. Lett. 34, 2147-2160.
44. Golds, T., Maliga, P., and, Koop, H.-U., (1993) Stable plastid transformation in PEG-treated protoplasts of Nicotiana tabacum. Biotechnology, 11, 95-97.
45. 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, 4083-4089.
46. Goodenough, U., Blaby, I., Casero, D., et al.,. (2014) The path to triacylglyceride obesity in the sta6 strain of Chlamydomonas reinhardtii. Eukaryot. Cell, 13, 591-613.
47. Goodstein, D.M., Shu, S., Howson, R., et al.,. (2012) Phytozome: a comparative platform for green plant genomics. Nucleic Acids Res. 40, D1178-D1186.
48. Hamilton, M.L., Haslam, R.P., Napier, J.A., and, Sayanova, O., (2014) Metabolic engineering of Phaeodactylum tricornutum for the enhanced accumulation of omega-3 long chain polyunsaturated fatty acids. Metab. Eng. 22, 3-9.
49. Harris, E.H., (2001) Chlamydomonas as a model organism. Plant Biol. 52, 363-406.
50. Helliwell, K.E., Scaife, M.A., Sasso, S., Araujo, A.P.U., Purton, S., and, Smith, A.G., (2014) Unraveling vitamin B12-responsive gene regulation in algae. Plant Physiol. 165, 388-397.
51. Hippler, M., Klein, J., Fink, A., Allinger, T., and, Hoerth, P., (2001) Towards functional proteomics of membrane protein complexes: analysis of thylakoid membranes from Chlamydomonas reinhardtii. Plant J. 28, 595-606.
52. Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M., and, Sakaki, Y., (2001) A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl Acad. Sci. USA, 98, 4569-4574.
53. Iwai, M., Ikeda, K., Shimojima, M., and, Ohta, H., (2014) Enhancement of extraplastidic oil synthesis in Chlamydomonas reinhardtii using a type-2 diacylglycerol acyltransferase with a phosphorus starvation-inducible promoter. Plant Biotechnol. J. 12, 808-819.
54. Jiang, W., Brueggeman, A.J., Horken, K.M., Plucinak, T.M., and, Weeks, D.P., (2014) Successful transient expression of Cas9/sgRNA genes in Chlamydomonas reinhardtii. Eukaryot. Cell, 13, 1465-1469.
55. Johnson, X., and, Alric, J., (2013) Central carbon metabolism and electron transport in Chlamydomonas reinhardtii: metabolic constraints for carbon partitioning between oil and starch. Eukaryot. Cell, 12, 776-793.
56. Juan, D., Pazos, F., and, Valencia, A., (2008) High-confidence prediction of global interactomes based on genome-wide coevolutionary networks. Proc. Natl Acad. Sci. USA, 105, 934-939.
57. Juhas, M., Eberl, L., and, Glass, J.I., (2011) Essence of life: essential genes of minimal genomes. Trends Cell Biol. 21, 562-568.
58. Kanehisa, M., (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27-30.
59. Kato, K., Marui, T., Kasai, S., and, Shinmyo, A., (2007) Artificial control of transgene expression in Chlamydomonas reinhardtii chloroplast using the lac regulation system from Escherichia coli. J. Biosci. Bioeng. 104, 207-213.
60. Keasling, J.D., (2012) Synthetic biology and the development of tools for metabolic engineering. Metab. Eng. 14, 189-195.
61. Keller, L.C., Romijn, E.P., Zamora, I., Yates, J.R., and, Marshall, W.F., (2005) Proteomic analysis of isolated Chlamydomonas centrioles reveals orthologs of ciliary-disease genes. Curr. Biol. 15, 1090-1098.
62. Khalil, A.S., and, Collins, J.J., (2010) Synthetic biology: applications come of age. Nat. Rev. Genet. 11, 367-379.
63. Kindle, K.L., (1990) High-frequency nuclear transformation of Chlamydomonas reinhardtii. Proc. Natl Acad. Sci. USA, 87, 1228-1232.
64. Kindle, K., Schnell, R., Fernandez, E., and, Lefebvre, P., (1989) Stable nuclear transformation of Chlamydomonas using the Chlamydomonas gene for nitrate reductase. J. Cell Biol. 109, 2589-2601.
65. Kindle, K.L., Richards, K.L., and, Stern, D.B., (1991) Engineering the chloroplast genome: techniques and capabilities for chloroplast transformation in Chlamydomonas reinhardtii. Proc. Natl Acad. Sci. USA, 88, 1721-1725.
66. Klein-Marcuschamer, D., Chisti, Y., Benemann, J.R., and, Lewis, D., (2013) A matter of detail: assessing the true potential of microalgal biofuels. Biotechnol. Bioeng. 110, 2317-2322.
67. Kliphuis, A.M., Klok, A.J., Martens, D.E., Lamers, P.P., Janssen, M., and, Wijffels, R.H., (2012) Metabolic modeling of Chlamydomonas reinhardtii: energy requirements for photoautotrophic growth and maintenance. J. Appl. Phycol. 24, 253-266.
68. Klok, A.J., Lamers, P.P., Martens, D.E., Draaisma, R.B., and, Wijffels, R.H., (2014) Edible oils from microalgae: insights in TAG accumulation. Trends Biotechnol. 32, 521-528.
69. Knight, T., (2003) Idempotent vector design for standard assembly of Biobricks. MIT Synthetic Biology Working Group Technical Reports. http://hdl.handle.net/1721.1/21168.
70. Koornneef, M., Alonso-Blanco, C., and, Vreugdenhil, D., (2004) Naturally occurring genetic variation in Arabidopsis thaliana. Annu. Rev. Plant Biol. 55, 141-172.
71. Kumar, S.V., Misquitta, R.W., Reddy, V.S., Rao, B.J., and, Rajam, M.V., (2004) Genetic transformation of the green alga-Chlamydomonas reinhardtii by Agrobacterium tumefaciens. Plant Sci. 166, 731-738.
72. Labadorf, A., Link, A., Rogers, M.F., Thomas, J., Reddy, A.S., and, Ben-Hur, A., (2010) Genome-wide analysis of alternative splicing in Chlamydomonas reinhardtii. BMC Genom. 11, 114.
73. Langevels, J.W.A., Dixon, J., and, Jaworski, J.F., (2010) Development perspectives of the biobased economy: a review. Crop Sci. 50, 142-151.
74. Lee, M.E., Aswani, A., Han, A.S., Tomlin, C.J., and, Dueber, J.E., (2013) Expression-level optimization of a multi-enzyme pathway in the absence of a high-throughput assay. Nucleic Acids Res. 41, 10668-10678.
75. Leõn, R., Couso, I., and, Fernández, E., (2007) Metabolic engineering of ketocarotenoids biosynthesis in the unicellular microalga Chlamydomonas reinhardtii. J. Biotechnol. 130, 143-152.
76. van Lis, R., Atteia, A., Mendoza-Hernández, G., and, González-Halphen, D., (2003) Identification of novel mitochondrial protein components of Chlamydomonas reinhardtii. A proteomic approach. Plant Physiol. 132, 318-330.
77. Lumbreras, V., Stevens, D.R., and, Purton, S., (1998) Efficient foreign gene expression in Chlamydomonas reinhardtii mediated by an endogenous intron. Plant J. 14, 441-447.
78. Lv, H., Qu, G., Qi, X., Lu, L., Tian, C., and, Ma, Y., (2013) Transcriptome analysis of Chlamydomonas reinhardtii during the process of lipid accumulation. Genomics, 101, 229-237.
79. Ma, S.M., Garcia, D.E., Redding-Johanson, A.M., et al.,. (2011) Optimization of a heterologous mevalonate pathway through the use of variant HMG-CoA reductases. Metab. Eng. 13, 588-597.
80. Maliga, P., (2012) Plastid Transformation in Flowering plants. In Genomics of Chloroplasts and Mitochondria (, Bock, R., and, Knoop, V.E., eds). the Netherlands: Springer, 35, 393-414.
81. Manichaikul, A., Ghamsari, L., Hom, E.F., et al.,. (2009) Metabolic network analysis integrated with transcript verification for sequenced genomes. Nat. Methods, 6, 589-592.
82. Manuell, A.L., Beligni, M.V., Elder, J.H., Siefker, D.T., Tran, M., Weber, A., McDonald, T.L., and, Mayfield, S.P., (2007) Robust expression of a bioactive mammalian protein in Chlamydomonas chloroplast. Plant Biotechnol. J. 5, 402-412.
83. Martin, V.J.J., Pitera, D.J., Withers, S.T., Newman, J.D., and, Keasling, J.D., (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat. Biotechnol. 21, 796-802.
84. 2 production by sulfur depletion. J. Biol. Chem. 284, 23415-23425.
85. May, P., Christian, J.-O., Kempa, S., and, Walther, D., (2009) ChlamyCyc: an integrative systems biology database and web-portal for Chlamydomonas reinhardtii. BMC Genom. 10, 209.
86. Mayfield, S.P., Franklin, S.E., and, Lerner, R.A., (2003) Expression and assembly of a fully active antibody in algae. Proc. Natl Acad. Sci. USA, 100, 438-442.
87. McIsaac, R.S., Gibney, P.A., Chandran, S.S., Benjamin, K.R., and, Botstein, D., (2014) Synthetic biology tools for programming gene expression without nutritional perturbations in Saccharomyces cerevisiae. Nucleic Acids Res. 42, 1-8.
88. Merchant, S.S., Prochnik, S.E., Vallon, O., et al.,. (2007) The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science, 318, 245-250.
89. Merchant, S.S., Kropat, J., Liu, B., Shaw, J., and, Warakanont, J., (2012) TAG, you're it! Chlamydomonas as a reference organism for understanding algal triacylglycerol accumulation. Curr. Opin. Biotechnol. 23, 352-363.
90. Michelet, L., Lefebvre-Legendre, L., Burr, S.E., Rochaix, J.-D., and, Goldschmidt-Clermont, M., (2011) Enhanced chloroplast transgene expression in a nuclear mutant of Chlamydomonas. Plant Biotechnol. J. 9, 565-574.
91. Molnar, A., Bassett, A., Thuenemann, E., Schwach, F., Karkare, S., Ossowski, S., Weigel, D., and, Baulcombe, D., (2009) Highly specific gene silencing by artificial microRNAs in the unicellular alga Chlamydomonas reinhardtii. Plant J. 58, 165-174.
92. Moulin, M., Nguyen, G.T.D.T., Scaife, M.A., Smith, A.G., and, Fitzpatrick, T.B., (2013) Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity. Proc. Natl Acad. Sci. USA, 110, 14622-14627.
93. Neumann, H., and, Neumann-Staubitz, P., (2010) Synthetic biology approaches in drug discovery and pharmaceutical biotechnology. Appl. Microbiol. Biotechnol. 87, 75-86.
94. Neupert, J., Karcher, D., and, Bock, R., (2009) Generation of Chlamydomonas strains that efficiently express nuclear transgenes. Plant J. 57, 1140-1150.
95. Nguyen, H.M., Baudet, M., Cuiné, S., et al.,. (2011) Proteomic profiling of oil bodies isolated from the unicellular green microalga Chlamydomonas reinhardtii: with focus on proteins involved in lipid metabolism. Proteomics, 11, 4266-4273.
96. Nickelsen, J., Van Dillewijn, J., Rahire, M., and, Rochaix, J., (1994) Determinants for stability of the chloroplast psbD RNA are located within its short leader region in Chlamydomonas reinhardtii. EMBO J. 1, 3182-3191.
97. Ning, J., Otto, T.D., Pfander, C., et al.,. (2013) Comparative genomics in Chlamydomonas and Plasmodium identifies an ancient nuclear envelope protein family essential for sexual reproduction in protists, fungi, plants, and vertebrates. Genes Dev. 27, 1198-1215.
98. Ohresser, M., Matagne, R.F., and, Loppes, R., (1997) Expression of the arylsulphatase reporter gene under the control of the nit1 promoter in Chlamydomonas reinhardtii. Curr. Genet. 31, 264-271.
99. Olson, E.J., Hartsough, L.A., Landry, B.P., Shroff, R., and, Tabor, J.J., (2014) Characterizing bacterial gene circuit dynamics with optically programmed gene expression signals. Nat. Methods, 11, 449-455.
100. Perrineau, M.-M., Gross, J., Zelzion, E., Price, D.C., Levitan, O., Boyd, J., and, Bhattacharya, D., (2014) Using natural selection to explore the adaptive potential of Chlamydomonas reinhardtii. PLoS One, 9, e92533.
101. Pitera, D.J., Paddon, C.J., Newman, J.D., and, Keasling, J.D., (2007) Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli. Metab. Eng. 9, 193-207.
102. Polle, J.E.W., Kanakagiri, S.-D., and, Melis, A., (2003) tla1, a DNA insertional transformant of the green alga Chlamydomonas reinhardtii with a truncated light-harvesting chlorophyll antenna size. Planta, 217, 49-59.
103. Prindle, A., Selimkhanov, J., Li, H., Razinkov, I., Tsimring, L.S., and, Hasty, J., (2014) Rapid and tunable post-translational coupling of genetic circuits. Nature, 508, 387-391.
104. Purton, S., and, Rochaix, J.D., (1995) Characterisation of the ARG7 gene of Chlamydomonas reinhardtii and its application to nuclear transformation. Eur. J. Phycol. 30, 141-148.
105. Quinn, J.M., and, Merchant, S., (1995) Two copper-responsive elements associated with the Chlamydomonas Cyc6 gene function as targets for transcriptional activators. Plant Cell, 7, 623-628.
106. Quintana, N., der Kooy, F.V., Van de Rhee, M.D., Voshol, G.P., and, Verpoorte, R., (2011) Renewable energy from cyanobacteria: energy production optimization by metabolic pathway engineering. Appl. Microbiol. Biotechnol. 91, 471-490.
107. Ramundo, S., Rahire, M., Schaad, O., and, Rochaix, J.-D., (2013) Repression of essential chloroplast genes reveals new signaling pathways and regulatory feedback loops in Chlamydomonas. Plant Cell 25, 167-186.
108. Randolph-Anderson, B.L., Boynton, J.E., Gillham, N.W., Harris, E.H., Johnson, A.M., Dorthu, M.-P., and, Matagne, R.F., (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. 236-236, 235-244.
109. Rasala, B.A., and, Mayfield, S.P., (2014) Photosynthetic biomanufacturing in green algae; production of recombinant proteins for industrial, nutritional, and medical uses. Photosynth. Res. DOI 10.1007/s11120-014-9994-7.
110. Rasala, B.A., Muto, M., Lee, P.A., et al.,. (2010) Production of therapeutic proteins in algae, analysis of expression of seven human proteins in the chloroplast of Chlamydomonas reinhardtii. Plant Biotechnol. J. 8, 719-733.
111. Rasala, B.A., Muto, M., Sullivan, J., and, Mayfield, S.P., (2011) Improved heterologous protein expression in the chloroplast of Chlamydomonas reinhardtii through promoter and 5' untranslated region optimization. Plant Biotechnol. J. 9, 674-683.
112. Rasala, B.A., Lee, P.A., Shen, Z., Briggs, S.P., Mendez, M., and, Mayfield, S.P., (2012) Robust expression and secretion of Xylanase1 in Chlamydomonas reinhardtii by fusion to a selection gene and processing with the FMDV 2A peptide. J. W. Stiller, ed. PLoS One, 7, e43349.
113. Rasala, B.A., Barrera, D.J., Ng, J., et al.,. (2013) Expanding the spectral palette of fluorescent proteins for the green microalga Chlamydomonas reinhardtii. Plant J. 74, 545-556.
114. Reijnders, M.J.M.F., van Heck, R.G.A., Lam, C.M.C., Scaife, M.A., dos Santos, V.A.P.M., Smith, A.G., and, Schaap, P.J., (2014) Green genes: bioinformatics and systems-biology innovations drive algal biotechnology. Trends Biotechnol. 32, 617-626.
115. Remacle, C., Cline, S., Boutaffala, L., Gabilly, S., Larosa, V., Barbieri, M.R., Coosemans, N., and, Hamel, P.P., (2009) The ARG9 gene encodes the plastid-resident N-acetyl ornithine aminotransferase in the green alga Chlamydomonas reinhardtii. Eukaryot. Cell, 8, 1460-1463.
116. Riaño-Pachón, D.M., Corrêa, L.G.G., Trejos-Espinosa, R., and, Mueller-Roeber, B., (2008) Green transcription factors: a Chlamydomonas overview. Genetics, 179, 31-39.
117. Ruecker, O., Zillner, K., Groebner-Ferreira, R., and, Heitzer, M., (2008) Gaussia-luciferase as a sensitive reporter gene for monitoring promoter activity in the nucleus of the green alga Chlamydomonas reinhardtii. Mol. Genet. Genomics, 280, 153-162.
118. Russa, M.La., Bogen, C., Uhmeyer, A., Doebbe, A., Filippone, E., Kruse, O., and, Mussgnug, J.H., (2012) Functional analysis of three type-2 DGAT homologue genes for triacylglycerol production in the green microalga Chlamydomonas reinhardtii. J. Biotechnol. 162, 13-20.
119. Sakamoto, W., Kindle, K.L., and, Stern, D.B., (1993) In vivo analysis of Chlamydomonas chloroplast petD gene expression using stable transformation of beta-glucuronidase translational fusions. Proc. Natl Acad. Sci. USA, 90, 497-501.
120. Scharff, L.B., and, Bock, R., (2014) Synthetic biology in plastids. Plant J. 78, 783-798.
121. Schmollinger, S., Strenkert, D., and, Schroda, M., (2010) An inducible artificial microRNA system for Chlamydomonas reinhardtii; confirms a key role for heat shock factor 1 in regulating thermotolerance. Curr. Genet. 56, 383-389.
122. Schroda, M., Blocker, D., and, Beck, C., (2000) The HSP70A promoter as a tool for the improved expression of transgenes in Chlamydomonas. Plant J. 21, 121-131.
123. Scott, S.A., Davey, M.P., Dennis, J.S., Horst, I., Howe, C.J., Lea-Smith, D.J., and, Smith, A.G., (2010) Biodiesel from algae: challenges and prospects. Curr. Opin. Biotechnol. 21, 277-286.
124. Shimogawara, K., Fujiwara, S., Grossman, A., and, Usuda, H., (1998) High-efficiency transformation of Chlamydomonas reinhardtii by electroporation. Genetics, 148, 1821-1828.
125. Sizova, I.A., Lapina, T.V., Frolova, O.N., Alexandrova, N.N., Akopiants, K.E., and, Danilenko, V.N., (1996) Stable nuclear transformation of Chlamydomonas reinhardtii with a Streptomyces rimosus gene as the selective marker. Gene, 181, 13-18.
126. Sizova, I., Greiner, A., Awasthi, M., Kateriya, S., and, Hegemann, P., (2013) Nuclear gene targeting in Chlamydomonas using engineered zinc-finger nucleases. Plant J. 73, 873-882.
127. Stevens, D.R., Rochaix, J.D., and, Purton, S., (1996) The bacterial phleomycin resistance gene ble as a dominant selectable marker in Chlamydomonas. Mol. Gen. Genet. 251, 23-30.
128. Stolc, V., Samanta, M.P., Tongprasit, W., and, Marshall, W.F., (2005) Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes. Proc. Natl Acad. Sci. USA, 102, 3703-3707.
129. Tissot-Lecuelle, G., Purton, S., Dubald, M., and, Goldschmidt-Clermont, M.P., (2014). Synthesis of recombinant products in the chloroplast. In Plastid Biology (eds., Theg, S.M., and, Wollman, F.-A.,). New York: Springer, pp. 517-558.
130. Tong, A.H., Evangelista, M., Parsons, A.B., et al.,. (2001) Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science, 294, 2364-2368.
131. Vajo, Z., Fawcett, J., and, Duckworth, W.C., (2001) Recombinant DNA technology in the treatment of diabetes: insulin analogs. Endocr. Rev. 22, 706-717.
132. Vilanova, C., and, Porcar, M., (2014) iGEM 2.0-refoundations for engineering biology. Nat. Biotechnol. 32, 420-424.
133. Villand, P., Eriksson, M., and, Samuelsson, G., (1997) Carbon dioxide and light regulation of promoters controlling the expression of mitochondrial carbonic anhydrase in Chlamydomonas reinhardtii. Biochem. J. 327, 51-57.
134. Wang, Z.T., Ullrich, N., Joo, S., Waffenschmidt, S., and, Goodenough, U., (2009) Algal lipid bodies: stress induction, purification, and biochemical characterization in wild-type and starchless Chlamydomonas reinhardtii. Eukaryot. Cell, 8, 1856-1868.
135. Wijffels, R.H., Kruse, O., and, Hellingwerf, K.J., (2013) Potential of industrial biotechnology with cyanobacteria and eukaryotic microalgae. Curr. Opin. Biotechnol. 24, 405-413.
136. Winzeler, E.A., Shoemaker, D.D., Astromoff, A., et al.,. (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science, 285, 901-906.
137. Wu, S., Xu, L., Huang, R., and, Wang, Q., (2011) Improved biohydrogen production with an expression of codon-optimized hemH and lba genes in the chloroplast of Chlamydomonas reinhardtii. Bioresour. Technol. 102, 2610-2616.
138. Xu, L., Wang, Q., Wu, S., and, Li, D., (2014) Improvement of hydrogen yield of lba-transgenic Chlamydomonas reinhardtii caused by increasing respiration and impairing photosynthesis. Int. J. Hydrogen Energy, 39, 13347-13352.
139. Yadav, V.G., De Mey, M., Lim, C.G., Ajikumar, P.K., and, Stephanopoulos, G., (2012) The future of metabolic engineering and synthetic biology: towards a systematic practice. Metab. Eng. 14, 233-241.
140. Yofe, I., Zafrir, Z., Blau, R., Schuldiner, M., Tuller, T., Shapiro, E., and, Ben-Yehezkel, T., (2014) Accurate, model-based tuning of synthetic gene expression using introns in S. cerevisiae. G. P. Copenhaver, ed. PLoS Genet. 10, e1004407.
141. Yoon, H.S., Hackett, J.D., Ciniglia, C., Pinto, G., and, Bhattacharya, D., (2004) A molecular timeline for the origin of photosynthetic eukaryotes. Mol. Biol. Evol. 21, 809-818.
142. Young, R.E.B., and, Purton, S., (2014) Cytosine deaminase as a negative selectable marker for the microalgal chloroplast: a strategy for the isolation of nuclear mutations that affect chloroplast gene expression. Plant J. 80, 915-925.
143. Yu, C., Cao, Y., Zou, H., and, Xian, M., (2011) Metabolic engineering of Escherichia coli for biotechnological production of high-value organic acids and alcohols. Appl. Microbiol. Biotechnol. 89, 573-583.
144. Zhang, R., Patena, W., Armbruster, U., Gang, S.S., Blum, S.R., and, Jonikas, M.C., (2014) High-throughput genotyping of green algal mutants reveals random distribution of mutagenic insertion sites and endonucleolytic cleavage of transforming DNA. Plant Cell, 26, 1398-1409.
145. Zhao, T., Wang, W., Bai, X., and, Qi, Y., (2009) Gene silencing by artificial microRNAs in Chlamydomonas. Plant J. 58, 157-164.
146. Zhao, Z., Guo, C., Sutharzan, S., Li, P., Echt, C.S., Zhang, J., and, Liang, C., (2014a) Genome-wide analysis of tandem repeats in plants and green algae. G3 (Bethesda), 4, 67-78.
147. Zhao, Z., Wu, X., Raj Kumar, P.K., Dong, M., Ji, G., Li, Q.Q., and, Liang, C., (2014b) Bioinformatics analysis of alternative polyadenylation in green alga Chlamydomonas reinhardtii using transcriptome sequences from three different sequencing platforms. G3 (Bethesda), 4, 871-883.