Bioactive and Novel Chemicals from Microalgae

Handbook of Microalgal Culture: Applied Phycology and Biotechnology: Second Edition

Volumn , Issue , 2013, Pages 504-531

  Coates, R Cameron ^a   Trentacoste, Emily ^a   Gerwick, William H ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

biofuels; cyanobacteria; hydrocarbons; lipids; microalgae; oxylipins; pigments; polyunsaturated fatty acids; secondary metabolites

Indexed keywords

ALGAE; BIOCHEMISTRY; BIOFUELS; BIOMOLECULES; BIOSYNTHESIS; CHEMICALS; HYDROCARBONS; LIPIDS; MICROORGANISMS; PIGMENTS; POLYUNSATURATED FATTY ACIDS;

CHEMICAL CLASS; CYANOBACTERIA; GENETIC MANIPULATIONS; GROWING DEMAND; MICRO-ALGAE; OXYLIPINS; PETROLEUM-DERIVED FUELS; SECONDARY METABOLITES;

METABOLITES;

EID: 84886975195     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781118567166.ch26     Document Type: Chapter

References (149)

1. Andreou, A., Brodhun, F. & Feussner, I. (2009) Biosynthesis of oxylipins in non-mammals. Prog. Lipid Res. 48: 148-170.
2. Andrianarison, R.H. & Beneytout, J.L. (1989) An enzymatic conversion of lipoxygenase products by a hydroperoxide lyase in blue-green algae (Oscillatoria sp.). Plant Physiol. 91: 1280-1287.
3. Appleton, D.R., Sewell, M.A., Berridge, M.V. & Copp, B.R. (2002) A new biologically active malyngamide from a New Zealand collection of the sea hare Bursatella leachii. J. Nat. Prod. 65: 630-631.
4. Asada, Y., Miyake, M., Miyake, J., Kurane, R. & Tokiwa, Y. (1999) Photosynthetic accumulation of poly-(hydroxybutyrate) by cyanobacteria -the metabolism andpotential for CO2 recycling. Int. J. Biol. Macromol. 25: 3742.
5. Baden, D.G. (1989) Brevetoxins: unique polyether dinoflag-ellate toxins. FASEB J. 3: 1807-1817.
6. Balaban, A.T. (1983) Topological indices based on topological distances in molecular graphs. Pure Appl. Chem. 55: 199-206.
7. Banarjee, A., Sharma, R., Chisti, Y. & Banarjee, U.C. (2002) Botryococcus braunii: a renewable source of hydrocarbons and other chemicals. Crit. Rev. Biotechnol. 22: 245-279.
8. Bardia, A., Tleyjeh, I.M., Cerhan, J.R., Sood, A.K., Limburg, P.J., Erwin, P.J. & Montori, V.M. (2008) Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin. Proc. 83: 23-34.
9. Basarab, G.S., Baker, D.R. & Fenyes, J.G. (1995) Bioassays in the discovery process of agrochemicals. In: Synthesis and Chemistry of Agrochemicals IV, ACS Symposium Series, Vol. 584 (eds D.R. Baker, J.G. Fenyes & G.S. Basarab), pp. 1-14. American Chemical Society, Washington, DC.
10. Bauer, I., Maranda, L., Young, K.A., Shimizu, Y., Fairchild, C., Cornell, L., MacBeth, J. & Huang, J. (1995) Isolation and structure of caribenolide I, a highly potent antitumor macrolide from a cultured free-swimming Caribbean dinoflagellate. Amphidinium sp. S1-36-5. J. Org. Chem. 60: 1084-1086.
11. BBC Research (2011) The global market for carotenoids. Available at http://www.bccresearch.com/report/carote noids-global-market-fod025d.html. Accessed on 14 February 2012.
12. Becker, W. (2004) Microalgae in human and animal nutrition. In: Handbook of Microalgal Culture: Biotechnology and Applied Phycology (ed. A. Richmond), pp. 312-351. Blackwell Publishing Ltd, Oxford.
13. Bergmann, S., Schuemann, J., Scherlach, K., Lange, C., Brakhage, A.A. & Hertweck, C. (2007) Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat. Chem. Biol. 3: 213-217.
14. Bhat, S.R. (2005) Chlorophyll: the wonder pigment. Science Reporter 42, 29-32. Available at http://drs.nio.org/ drs/bitstream/2264/426/1/Sci_Rep_42_29.pdf. Accessed on 14 February 2012.
15. Blokhin, A.V., Yoo, H.D., Geralds, R.S., Nagle, D.G., Gerwick, W.H. & Hamel, E. (1995) Characterization of the interaction of the marine cyanobacterial natural product curacin A with the colchicine site of tubulin and initial structure-activity studies with analogs. Mol. Pharmacol. 48: 523-531.
16. Blomquist, G.J. & Bagneres, A.G. (eds) (2010) Insect Hydrocarbons: Biology, Biochemistry, and Chemical Ecology. Cambridge University Press, New York.
17. Boettcher, T., Pitscheider, M. & Sieber, S.A. (2010) Natural products and their biological targets: proteomic and metabolomic labeling strategies. Angew. Chem. Int. Ed. 49: 2680-2698.
18. Bokesch, H.R., O'Keefe, B.R., McKee, T.C., Pannell, L.K., Patterson, G.M., Gardella, R.S., Sowder, R.C., Turpin, J., Watson, K., BuckheitJr, R.W. & Boyd, M.R. (2003) A potent novel anti-HIV protein from the cultured cyanobacterium Scytonema varium. Biochemistry 42: 2578-2584.
19. Boyd, M.R., Gustafson, K.R., McMahon, J.B., Shoemaker, R.H., O'Keefe, B.R., Mori, T., Gulakowski, R.J., Wu, L., Rivera, M.I., Laurencot, C.M., et al. (1997) Discovery of cyanovirin-N, a novel human immunodeficiency virusinactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrob. Agents Chemother. 41: 1521-1530.
20. Breinholt, V., Schimerlik, M., Dashwood, R. & Bailey, G. (1995) Mechanisms of chlorophyllin anticarcinogenesis against aflatoxin B1: complex formation with the carcinogen. Chem. Res. Toxicol. 8: 506-514.
21. Cambell III, J., Stevens Jr., S.E. & Balkwill, D.L. (1982) Accu-mulation of poly-3-hydroxybutyrate in Spirulina platensis. J. Bacteriol. 149: 361-363.
22. Capon, R.J., Dunlop, R.W., Ghisalberti, E.L. & Jefferies, P.R. (1983) Poly-3-hydroyalkanoates from marine and freshwater cyanobacteria. Phytochemistry 22: 1181-1184.
23. Carr, N.G. (1966) The occurrence of poly-ß-hydroxy-butyrate in the blue-green algae. Chlorogleoea frischii. Biochim. Bip-phys. Acta 120: 308-310.
24. Chang, Z., Flatt, P., Gerwick, W.H., Nguyen, V.A., Willis, C.L. & Sherman, D.H. (2002) The barbamide biosynthetic gene cluster: a novel marine cyanobacterial system of mixed polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) origin involving an unusual trichloroleucyl starter unit. Gene 296: 235-247.
25. Chanprateep, S. (2010) Current trends in biodegradable poly-hydroxyalkanoates. J. Biosci. Bioeng. 110: 621-632.
26. Cheng, K., Wong, C., Wang, M., He, Q. & Chen, F. (2009) Identification and characterization of molecular targets of natural products by mass spectrometry. Mass Spectrom. Rev. 29: 126-155.
27. Chi, X., Yang, Q., Zhao, F., Qin, S., Yang, Y., Shen, J. & Lin, H. (2008) Comparative analysis of fatty acid desaturases in cyanobacterial genomes. Comp. Funct. Genomics. doi: 10.1155/2008/284508.
28. Chisti, Y. (2007) Biodiesel from microalgae. Biotechnol. Adv. 25: 294-306.
29. Clinton, S.K. (1998) Lycopene: chemistry, biology, and implications for human health and disease. Nutr. Rev. 56: 35-51.
30. Cooper, D. (2004) Carotenoids in health and disease: recent scientific evaluations, research recommendations and the consumer. J. Nutr. 134: 221S-224S.
31. Creton, B., Dartiguelongue, C., Bruin, T. & Toulhoat, H. (2010) Prediction of the cetane number of diesel compounds using the quantitative structure property relationship. Energy Fuels 24: 5396-5403.
32. Crews, P., Rodriguez, J. & Jaspars, M. (2010) Organic Structure Analysis, 2nd edn. Oxford University Press, New York.
33. 1 and two heterocyclic amines in the Salmonella mutagenicity assay. Carcinogenesis 12: 939-942.
34. Dashwood, R., Yamane, S. & Larsen, R. (1996) Study of the forces stabilizing complexes between chlorophylls and heterocyclic amine mutagens. Environ. Mol. Mutagen. 27: 211-218.
35. Dayan, F.E., Owens, D.K. & Duke, S.O. (2012) Rational for a natural products approach to herbicide discovery. Pest Manage. Sci. 68(4): 519-528.
36. Del Campo, J. & Garcia-Gonzalez, M. (2007) Outdoor cultivation of microalgae for carotenoid production: current state and perspectives. Appl. Microbiol. Biotechnol. 74: 1163-1174.
37. Dennis, M.W. & Kolattukudy, P.E. (1991) Alkane biosynthesis by decarbonylation of aldehyde catalyzed by a microsomal preparation from Botryococcus braunii. Arch. Biochem. Biophys. 287: 268-275.
38. Doan, T.T.P., Carlsson, A.S., Hamberg, M., Bulow, L., Stymne, S. & Olsson, P. (2009) Functional expression of five Arabidopsis fatty acyl-CoA reductase genes in Escherichia coli. J. Plant Physiol. 166: 787-796.
39. Donia, M.S., Hathaway, B.J., Sudek, S., Haygood, M.G., Rosovitz, M.J., Ravel, J. & Schmidt, E.W. (2006) Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nat. Chem. Biol. 2: 729-735.
40. Egner, P.A., Wang, J.B., Zhu, Y.R., Zhang, B.C., Wu, Y., Zhang, Q.N., Qian, G.S., Kuang, S.Y., Gange, S.J., Jacobson, L.P., Helzlsouer, K.J., Bailey, G.S., Groop-man, J.D. & Kensler T.W. (2001) Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc. Natl. Acad. Sci. USA 98: 14601-14606.
41. Engene, N., Rottacker, E.C., Kastovsky, J., Byrum, T., Choi, H., Ellisman, M.H., Komárek, J. & Gerwick, W.H. (2011). Moorea producta gen. nov., sp. nov. and Moorea bouillonii comb. nov., tropical marine cyanobacteria rich in bioactive secondary metabolites. Int. J. Syst. Evol. Microbiol. doi: 10.1099/ijs.0.033761-0.
42. Eser, B.E., Das, D., Han, J., Jones, P.R. & Marsh, E.N. (2011) Oxygen-independent alkane formation by non-heme iron-dependent cyanobacterial aldehyde decarbonylase: investigation of kinetics and requirement for an external electron donor. Biochemistry 50: 10743-10750.
43. 3]methionine into 7-and 8-methylheptadecanes. Biochemistry 9: 418-422.
44. 14C]adenosylmethionine. Biochemistry 11: 2411-2416.
45. Foley, P.M., Beach, E.S. & Zimmerman, J.B. (2011) Algae as a source of renewable chemicals: opportunities and challenges. Green Chem. 13: 1399-1405.
46. Gehret, L.J., Gu, L., Gerwick, W.H., Wipf, P., Sherman, D.H. & Smith, J.L. (2011) Terminal alkene formation by the thioesterase of curacin A biosynthesis. Structure of a decarboxylating thioesterase. J. Biol. Chem. 286: 14445-14454.
47. Gehret-McCarthy, J., Eisman, E.B., Kulkarni, S., Gerwick, L., Gerwick, W.H., Wipf, P., Sherman, D.H. & Smith, J.L. (2012) Structural basis of functional group activation by sulfotransferases in complex metabolic pathways. ACS Chem. Biol. doi: 10.1021/cb300385.
48. Gerwick, W.H. (1994) Structure and biosynthesis of marine oxylipins. Biochim. Biophys. Acta 1211: 242-255.
49. Giessen, T.W. & Marahiel, M.A. (2012) Ribosome-independent biosynthesis of biologically active peptides: application of synthetic biology to generate structural diversity. FEBSLett. doi: 10.1016/j.febslet.2012.01.017.
50. 14C]stearate. Biochim. Biophys. Acta 711: 261-265.
51. Grindberg, R.V., Ishoey, T., Brinza, D., Esquenazi, E., Coates, R.C., Liu, W.T., Gerwick, L., Dorrestein, P.C., Pevzner, P., Lasken, R. & Gerwick, W.H. (2011) Single cell genome amplification accelerates identification of the Apratoxin biosynthetic pathway from a complex microbial assemblage. PLoS ONE 6: e18565. doi: 10.1371/jour-nal.pone.0018565.
52. Guerin, M., Huntley, M. & Olaizola, M. (2003) Haematococ-cus astaxanthin: applications for human health and nutrition. Trends Biotechnol. 21: 210-216.
53. Guschina, I.A. & Harwood, J.L. (2006) Lipids and lipid metabolism in eukaryotic algae. Prog. Lipid Res. 45: 160-186.
54. Guzman, S., Gato, A., Lamela, M., Freire-Garabal, M. & Calleja, J.M. (2003) Anti-inflammatory and immunomodulatory activities of polysaccharide from Chlorella stigmat-aphora and Phaeodactylum tricornutum. Phytother. Res. 17: 665-670.
55. Han, J., McCarthy, E.D., Calvin, M. & Benn, M.H. (1968) Hydrocarbon constituents of the blue-green algae Nostoc muscorum, Anacystis nidulans, Phormidium luridum and Chlorogloea fritschii. J. Chem. Soc. C: 2785-2791.
56. Han, J., Chan, H. W. & Calvin, M. (1969) Biosynthesis of alkanes in Nostoc muscorum. J. Am. Chem. Soc. 91: 5156-5159.
57. Hauvermale, A.J., Kuner, J., Rosenzweig, B., Guerra, D., Diltz, S. & Metz, J.G. (2006) Fatty acid production in Schizochytrium sp.: involvement of a polyunsaturated fatty acid synthase and a type I fatty acid synthase. Lipids 41(8): 739-747.
58. Hayashi, T. & Hayashi, K. (1996) Calcium spirulan, an inhibitor of enveloped virus replication, from a blue-green alga Spirulinaplatensis. J. Nat. Prod. 59: 83-87.
59. Hoffman, V. (2009) What you don't know can hurt you: micronutrient content and fungal contamination of foods in developing countries. Agric. Res. Econ. Rev. 38: 100-108.
60. Hussein, G., Sankawa, U., Goto, H., Matsumoto, K. & Watan-abe, H. (2006) Astaxanthin, a carotenoid with potential in human health and nutrition. J. Nat. Prod. 69: 443-449.
61. Innis, S.M. (2008) Dietary omega 3 fatty acids and the developing brain. Brain Res. 1237: 35-43.
62. Jaswir, I., Noviendri, D., Hasrini, R.F. & Octavianti, F. (2011) Carotenoids: sources, medicinal properties and their application in food and nutraceutical industry. J. Med. Plants Res. 5: 7119-7131.
63. Jones, C. & Mayfield, S.P. (2011) Algae biofuels: versatility for the future of bioenergy. Curr. Opin. Biotechnol. 23: 1-6.
64. Jones, A.C., Monroe, E.A., Podell, S., Hess, W.R., Klages, S., Esquenazi, E., Niessen, S., Hoover, H., Rothmann, M., Lasken, R.S, Yates, J.R., 3rd, Reinhardt, R., Kube, M., Burkart, M.D., Allen, E.E., Dorrestein, P.C., Gerwick, W.H. & Gerwick, L. (2011) Genomic insights into the physiology and ecology of the marine filamentous cyanobacterium Lyngbya majuscula. Proc. Natl. Acad. Sci. USA 108: 8815-8820.
65. Kanekiyo, K., Lee, J., Hayashi, K., Takenaka, H., Hayakawa, Y., Endo, S. & Hayashi, T. (2005) Isolation of an antiviral polysaccharide, nostoflan, from a terrestrial cyanobacterium Nostoc flagelliforme. J. Nat. Prod. 68: 1037-1041.
66. Kasper, A.C., Baker, J.B., Kim, H. & Hong, J. (2009) The end game of chemical genetics: target identification. Future Med. Chem. 1: 727-736.
67. Kensler, T.W., Groopman, J.D. & Roebuck, B.D. (1998) Use of aflatoxin adducts as intermediate endpoints to assess the efficacy of chemopreventive interventions in animals and man. Mutat. Res. 402: 165-172.
68. Kersten, R.D., Yang, Y.L., Xu, Y., Cimermancic, P., Nam, S.J., Fenical, W., Fischbach, M.A., Moore, B.S. & Dorrestein, P.C. (2011) A mass spectrometry-guided genome mining approach for natural product peptidogenomics. Nat. Chem. Biol. 7: 794-802.
69. Kobayashi, J. (2008) Amphidinolides and its related macrolides form marine dinoflagellates. J. Antibiot. 6: 271-284.
70. Kolattukudy, P.E. (1967) Biosynthesis of paraffins in Brassica oleraceae: fatty acid elongation-decarboxylation as a plausible pathway. Phytochemistry 6: 963-975.
71. Kubanek, J., Snell, T.W. & Pirkle, C. (2007) Chemical defense of the red tide dinoflagellate Karenia brevis against rotifer grazing. Limnol. Oceanogr. 52: 1026-1035.
72. Kurokawa, M., Shimizu, T., Watanabe, W. & Shiraki, K. (1975) Development of new antiviral agents from natural products. Open Antimicrob. Agents J. 2: 49-57.
73. Lane, A.L. & Moore, B.S. (2011) A sea of biosynthesis: marine natural products meet the molecular age. Nat. Prod. Rep. 28: 411-428.
74. Lang, I. & Feussner, I. (2007) Oxylipin formation in Nostoc punctiforme (PCC73102). Phytochemistry 68: 1120-1127.
75. Lee, D.-S., Nioche, P., Hamberg, M. & Raman, C.S. (2008) Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes. Nature 455(18): 363-370.
76. Li, Y., Han, D., Hu, G., Sommerfeld, M. & Hu, Q. (2010) Inhibition of starch synthesis results in overproduction of lipids in Chlamydomonas reinhardtii. Biotechnol. Bioeng. 107: 258-268.
77. Li, N., Nørgaard, H., Warui, D.M., Booker, S.J., Krebs, C. & Bollinger Jr, J.M. (2011) Conversion of fatty aldehydes to alka(e)nes and formate by a cyanobacterial aldehyde decarbonylase: cryptic redox by an unusual dimetal oxygenase. J. Am. Chem. Soc. 133: 6158-6161.
78. Li, N., Chang, W.C., Warui, D.M., Booker, S.J., Krebs, C. & Bollinger, J.M. Jr. (2012) Evidence for only oxygena-tive cleavage of aldehydes to alk(a/e)nes and formate by cyanobacterial aldehyde decarbonylases. Biochemistry 51: 7908-7916.
79. Luesch, H., Yoshida, W.Y., Moore, R.E., Paul, V.J. & Corbett, T.H. (2001) Total structure determination of apratoxin A, a potent novel cytotoxin from the marine cyanobacterium Lyngbya majuscula. J. Am. Chem. Soc. 123: 5418-5423.
80. Luesch, H., Chanda, S.K., Raya, R.M., DeJesus, P.D., Orth, A.P., Walker, J.R., Belmonte, J.C.I. & Schultz, P.G. (2005) A functional genomics approach to the mode of action of apratoxin A. Nat. Chem. Biol. 2: 158-167.
81. Markowitz, V.M., Chen, I.-M.A., Chu, K., Szeto, E., Pala-niappan, K., Grechkin, Y., Ratner, A., Jacob, B., Pati, A., Huntemann, M., Liolios, K., Pagani, I., Anderson, I., Mavromatis, K., Natalia, N., Ivanova, N.N. & Kyrpides, N.C. (2012) IMG/M: the integrated metagenome data management and comparative analysis system. Nucleic Acids Res. 40(D1): D123-D129.
82. Maschek, J.A. & Baker, B.J. (2009) The chemistry of algal secondary metabolism. In: Algal Chemical Ecology (ed. C.D. Amsler), pp. 1-24. Springer-Verlag, Berlin/Heidelberg.
83. Medina, R.A., Goeger, D.E., Hills, P., Mooberry, S.L., Huang, N., Romero, L.I., Ortega-Barría, E., Gerwick, W.H. & McPhail K.L. (2008) Coibamide A, a potent antiproliferative cyclic depsipeptide from the panamanian marine cyanobacterium Leptolyngbya sp. J. Am. Chem. Soc. 130: 6324-6325.
84. Mendez-Perez, D., Begemann, M.B. & Pfleger, B.F. (2011) Modular synthase-encoding gene involved in a- olefin biosynthesis in Synechococcus sp. strain PCC 7002. Appl. Environ. Microbiol. 77(12): 4264-4267.
85. Metzger, P. & Largeau, C. (2005) Botryococcus braunii: a rich source for hydrocarbons and related ether lipids. Appl. Microbiol. Biotechnol. 66: 486-496.
86. Mevers, E., Liu, W.T., Engene, N., Mohimani, H., Byrum, T., Pevzner, P.A., Dorrestein, P.C., Spadafora, C. & Gerwick, W.H. (2011) Cytotoxic veraguamides, alkynyl bromide containing cyclic depsipeptides from the marine cyanobacterium cf. Oscillatoria margaritifera. J. Nat. Prod. 74: 928-936.
87. Mooney, B.P. (2009) The second green revolution? Production of plant-based biodegradable plastics. Biochem. J. 418: 219-232.
88. Murakami, N., Shirahshi, A.N. & Sakakibara, J. (1992) Two unsaturated 9R-hydroxy fatty acids from the cyanobacterium Anabaena flos-aquae f. flos-aquae. Lipids 27: 776-778.
89. Mydlarz, L.D., Jacobs, R.S., Boehnlein, J. & Kerr, R.G. (2003) Pseudopterosin biosynthesis in Symbiodinium sp., the dinflagellate symbiont of Pseudopterogorgia elisa-bethae. Chem. Biol. 10: 1051-1056.
90. Naccarato, W.F., Gilbertson, J.R. & Gelman, R.A. (1974) Effects of different culture media and oxygen upon lipids of Escherichia coli K-12. Lipids 9(5): 322-327.
91. Nagle, D.G. & Paul, V.J. (1999) Production of secondary metabolites by filamentous tropical marine cyanobacteria: ecological functions of the compounds. J. Phycol. 35: 1412-1421.
92. Nakamura, H., Asari, T., Ohizumi, Y., Kobayashi, J., Yamasu, T. & Murai, A. (1993) Isolation of zooxanthellatoxins, novel vasoconstrictive substances from the zooxanthella Symobio-dinium sp. Toxicon 31: 371-376.
93. National Renewable Energy Laboratory (NREL) (1998) A look back at the U.S. Department of Energy's Aquatic Species Program -Biodiesel from Algae. U.S. Department of Energy, Office of Fuels Development. Available at http://www.nrel.gov/biomass/pdfs/24190.pdf. Accessed on 14 February 2012.
94. Nomisma Institute (2008) European agriculture of the future: the role of plant protection products. Available at http://www .nomisma.it/uploads/media/Executive_summary-20080124 _01.pdf. Accessed on 14 February 2012.
95. Palozza, P., Torelli, C., Boninsegna, A., Simone, R., Catalano, A., Mele, M.C. & Picci, N. (2009) Growth-inhibitory effects of the astaxanthin-rich alga Haematococcus pluvi-alis in human colon cancer cells. Cancer Lett. 283: 108-117.
96. Park, M.-O. (2005) New pathway for long-chain n-alkane synthesis via 1-alcohol in Vibrio furnissi M1. J. Bacteriol. 187(4): 1426-1429.
97. Pohnert, G. & Boland, W. (2002) The oxylipin chemistry of attraction and defense in brown algae and diatoms. Nat. Prod. Rep. 19: 108-122.
98. Poirier, Y., Nawrath, C. & Somerville, C. (1995) Production of polyhydroxyalkanoates, a family of biodegradable plastics and elastomers, in bacteria and plants. Nat. Biotech-nol. 13: 142-150.
99. Prabhu, P.N., Ashokkumar, P. & Sudhandiran, G. (2009) Antioxidative and antiproliferative effects of astaxanthin during the initiation stages of 1,2-dimethyl hydrazine-induced experimental colon carcinogenesis. Fund. Clin. Pharmacol. 23: 225-234.
100. Pratt, M.M., Reddy, A.P., Hendricks, J.D., Pereira, C., Kensler, T.W. & Bailey, G.S. (2007) The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l] pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers and final tumor outcome. Carcinogenesis 28: 611-624.
101. Radakovits, R., Jinkerson, R.E., Darzins, A. & Posewitz, M.C. (2010) Genetic engineering of algae for enhanced biofuel production. Eukaryot. Cell 9: 486-501.
102. Rehm, B.H.A. (2010) Bacterial polymers: biosynthesis, modifications and applications. Nat. Rev. Microbiol. 8: 578-592.
103. Ribeiro, R.D., Barreto, D.W. & Coelho, M.A.Z. (2011) Technological aspects of ß -carotene production. Food Bioprocess Technol. 4: 693-701.
104. Riekhof, W.R., Sears, B.B. & Benning, C. (2005) Annotation of genes involved in glycerolipid biosynthesis in Chlamy-domonas reinhardtii: discovery of the betaine lipid synthase BTA1Cr. Eukaryot. Cell 4: 242-252.
105. Rodriguez-Navarro, A.J., Lagos, N., Lagos, M., Braghetto, I., Csendes, A., Hamilton, J., Figueroa, C., Truan, D., Garcia, C., Rojas, A., Iglesias, V., Brunet, L. & Alvarez, F. (2007) Neosaxitoxin as a local anesthetic: preliminary observations from a first human trial. Anesthesiology 106: 339-345.
106. Roessler, P.G. (1990) Environmental control of glycerolipid metabolism in microalgae: commercial implications and future research directions. J. Phycol. 26: 393-399.
107. Rowland, S.J., Belt, S.T., Wraige, E.J., Masse, G., Rous-sakis, C. & Robert, J.M. (2001) Effects of temperature on polyunsaturation in cytostatic lipids of Haslea ostrearia. Phytochemistry 56: 597-602.
108. Rude, M.A., Baron, T.S., Brubaker, S., Alibhai, M., Del Cardayre, S.B. & Schirmer, S.B. (2011) Terminal olefin (1-alkene) biosynthesis by a novel P450 fatty acid decarboxylase from Jeotgalicoccus sp. Appl. Environ. Microbiol. 77: 1718-1727.
109. Sachs, J.P., Pahnke, K., Smittenberg, R. & Zhang, Z. (2007) Paleooceanography, biological proxies, biomarkers. In: Encyclopedia ofQuaternary Science (ed. S.A. Elias), pp. 1627-1634. Elsevier, Oxford. ISBN: 9780444527479, 10.1016/B0-44-452747-8/00313-6.
110. Saravanan, P., Davidson, N.C., Schmidt, E.B. & Calder, P.C. (2010) Cardiovascular effects of marine omega-3 fatty acids. Lancet 375: 540-550.
111. Schirmer, A., Rude, M.A., Li, X., Popova, E. & Cardayre, S. (2010) Microbial biosynthesis of alkanes. Science 329: 559-562.
112. Schlebusch, M. & Forchhammer, K. (2010) Requirement of the nitrogen starvation-induced protein Sll0783 for polyhydroxybutyrate accumulation in Synechocystis sp. strain PCC 6803. Appl. Environ. Microbiol. 76: 6101-6107.
113. Schmidt, E.W., Nelson, J.T., Rasko, D.A., Sudek, S., Eisen, J. A., Haygood, M.G. & Ravel, J. (2005) Patellamide A and C biosynthesis by microcin-like pathway in Procholon didmni, the cyanobacterial symbiont of Lissoclinum patella. Proc. Natl. Acad. Sci. USA 102: 7315-7320.
114. Schneider, C., Niisuke, K., Boeglin, W.E., Voehler, M., Stec, D.F., Porter, N.A. & Brash, A.R. (2007) Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120. Proc. Natl. Acad. Sci. USA 104: 18941-18945.
115. Sharma, L., Panda, B., Singh, A.K. & Mallick, N. (2006) Studies on poly-b-hydroxybutyrate synthase activity of Nostoc muscorum. J. Gen. Appl. Microbiol. 52: 209-214.
116. Shick, J.M. & Dunlap, W.C. (2002) Mycosporine-like amino acids and related gadusols: biosynthesis, accumulation, and UV-protective functions in aquatic organisms. Annu. Rev. Physiol. 64: 223-262.
117. Shifrin, N.S. & Chisholm, S.W. (1981) Phytoplankton lipids: interspecific differences and effects of nitrate, silicate and light-dark cycles. J. Phycol. 17: 374-384.
118. Shimizu, Y. (1996) Microalgal metabolites: a new perspective. Annu. Rev. Microbiol. 50: 431-465.
119. Shulse, C.N. & Allen, E.E. (2011) Widespread occurrence of secondary lipid biosynthesis potential in microbial lineages. PLoS ONE 6: e20146. doi: 10.1371/journal.pone. 0020146.
120. Siems, W., Wiswedel, I. Sommerburg, O., Langhans, C.-D., Salerno, C., Crifo, C., Capuozzo, E., Alija, A., Bresgen, N., Grune, T. & Eckl, P. (2005) Clinical use of carotenoids -antioxidative protection versus prooxidative side effects. In: Free Radicals and Diseases: Gene Expression, Cellular Metabolism and Pathophysiology, NATO Science Series, I: Life and Behavioural Sciences, Vol. 367 (ed. T. Grune), pp. 177-192. IOS Press. Amsterdam, The Netherlands.
121. Simmons, T.L., Coates, R.C., Clark, B.R., Engene, N., Gonzalez, D., Esquenazi, E., Dorrestein, P.C. & Gerwick, W.H. (2008) Biosynthetic origin of natural products isolated from marine microorganism-invertebrate assemblages. Proc. Natl. Acad. Sci. USA 105: 4587-4594.
122. Simmons, T.L. & Gerwick, W.H. (2008) Anticancer drugs of marine origin. In: Oceans and Human Health: Risk and Remedies from the Seas (eds P. Walsh, S. Smith, L. Fleming, H. Solo-Gabriele & H.W. Gerwick), pp. 431-452. Academic Press, St. Louis, MO.
123. Simonich, M.T., Egner, P.A., Roebuck, B.D., Orner, G.A., Jubert, C., Pereira, C., Groopman, J.D., Kensler, T.W., Dashwood, R.H., Williams, D.E. & Bailey, G.S. (2007) Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat. Carcinogenesis 28: 1294-1302.
124. Singh, P. & Goyal, G.K. (2008) Dietary lycopene: its properties and anticarcinogenic effects. Comp. Rev. Food Sci. Food Saf. 7: 255-270.
125. Singh, S., Kate, B.N. & Banerjee, U.C. (2005) Bioactivecom-pounds from cyanobacteria and microalgae: an overview. Crit. Rev. Biotechnol. 25: 73-95.
126. Singh, R.K., Tiwari, S.P., Rai, A.K. & Mohaptra, T.M. (2011) Cyanobacteria: an emerging source for drug discovery. J. Antibiotics 64: 401-412.
127. Stal, L.J. (1992) Poly(hydroxyalkanoate) in cyanobacteria: an overview. FEMSMicrobiol. Rev. 103: 169-180.
128. Stevenson, C.S., Capper, E.A., Roshak, A.K., Marquez, B., Eichman, C., Jackson, J.R., Mattern, M., Ger-wick, W.H., Jacobs, R.S. & Marshall, L.A. (2002a) The identification and characterization of the marine natural product scytonemin as a novel antiproliferative pharmacophore. J. Pharmacol. Exp. Ther. 303: 858-866.
129. Stevenson, C.S., Capper, E.A., Roshak, A.K., Marquez, B., Grace, K., Gerwick, W.H., Jacobs, R.S. & Marshall, L.A. (2002b) Scytonemin -a marine natural product inhibitor of kinases key in hperproliferative inflammatory diseases. Inflamm. Res. 51: 112-114.
130. Sudakin, D.L. (2003) Dietary aflatoxin exposure and chemo-prevention of cancer: a clinical review. J. Toxicol. Clin. Toxicol. 41: 195-204.
131. Takahashi, M., Ohizumi, Y. & Yasumoto, T. (1982) Maitotoxin, a Ca2+ channel activator candidate. J. Biol. Chem. 257: 7287-7289.
132. Takeda, S., Bando, N. & Yamanishi, R. (2008) Ingested beta-carotene enhances glutathione level and up-regulates the activity of cysteine cathepsin in murine splenocytes. Biosci. Biotechnol. Biochem. 72: 1595-1600.
133. Tan, L.T. (2010) Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery. J. Appl. Phycol. 22: 659-676.
134. Tan, X., Yao, L., Gao, Q., Wang, W., Qi, F. & Lu, X. (2011) Photosynthesis driven conversion of carbon dioxide to fatty alcohols and hydrocarbons in cyanobacteria. Metab. Eng. 13: 169-176.
135. U.S. Department of Energy [US DOE] (2010) National algal biofuels technology roadmap. U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy, Biomass Program.
136. U.S. Energy Information Administration [US EIA] (2012) Annual Energy Outlook 2012 Early Release Report. Available at http://www.eia.gov/forecasts/aeo/er/. Accessed on 13 February 2012.
137. Villa, F.A. & Gerwick, L. (2010) Marine natural product drug discovery: leads for treatment of inflammation, cancer, infections, and neurological disorders. Immunopharmacol. Immunotoxicol. 32: 228-237.
138. Villa, F.A., Lieske, K. & Gerwick, L. (2010) Selective MyD88-dependent pathway inhibition by the cyanobacterial natural product malyngamide F acetate. Eur. J. Pharmacol. 629: 140-146.
139. Von Braun, J. (2007) The world food situation: new driving forces and required actions. International Food Policy Research Institute (IFPRI), Washington, DC. Available at http://dx.doi.org/10.2499/0896295303. Accessed on 14 February 2012.
140. Warude, D., Joshi, K. & Harsulkar, A. (2006) Polyunsaturated fatty acids: biotechnology. Crit. Rev. Biotechnol. 26: 83-93.
141. Wiedenmann, J. (2008) Marine proteins. In: Oceans and Human Health. Risks and Remedies from the Sea (eds PJ. Walsh, S.L. Smith, L.E. Fleming, H.M. Solo-Gabriele & W.H. Gerwick), pp. 469-495. Academic Press, St. Louis, MO.
142. Wienkoop, S., Weiss, J., May, P., Kempa, S., Irgang, S., Recuenco-Munoz, L., Pietzke, M., Schwemmer, T., Rup-precht, J., Egelhofer, V. & Weckwerth, W. (2010) Targeted proteomics for Chlamydomonas reinhardtii combined with rapid subcellular protein fractionation, metabolomics and metabolic flux analyses. Mol. BioSyst. 6: 1018-1031.
143. Wild, C.P. & Gong, Y.Y. (2010) Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis 31: 71-82.
144. Winter, J.M. & Tang, Y. (2011) Synthetic biological approaches to natural product biosynthesis. Curr. Opin. Biotechnol. 23: 1-8.
145. Wolfe, D. (2009) Superfoods: The Food and Medicine of the Future. North Atlantic Books, California.
146. Wood, J.N. & James, B. (2005) Voltage-gated sodium channel blockers; target validation and therapeutic potential. Curr. Top. Med. Chem. 5: 529-537.
147. Work, V.H., Radakovits, R., Jinkerson, R.E., Meuser, J.E., Elliott, L.G., Vinyard, D.J., Laurens, L.M., Dismukes, G.C. & Posewitz, M.C. (2010) Increased lipid accumulation in the Chlamydomonas reinhardtii sta7-10 starchless isoamylase mutant and increased carbohydrate synthesis in complemented strains. Eukaryot. Cell 9: 1251-1261.
148. Zainuddin, E.N., Mentel, R., Wray, V., Jansen, R., Nimtz, M., Lalk, M. & Mundt, S. (2007) Cyclic depsipeptides, ichthyopeptins A and B, from Microcystis ichthyoblabe. J. Nat. Prod. 70: 1084-1088.
149. Zhang, L., Longley, R.E. & Koehn, F.E. (1997) Antiproliferative and immunosuppressive properties of microcolin A, a marine-derived lipopeptide. Life Sci. 6: 751-762.