Systems biology of cyanobacterial secondary metabolite production and its role in drug discovery

Expert Opinion on Drug Discovery

Volumn 3, Issue 8, 2008, Pages 903-929

  Wase, Nishikant V ^a   Wright, Phillip C ^a  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

Author keywords

Cyanobacteria; Docking; Drug discovery; Non ribosomal peptide synthetase; Polyketide synthase; Systems biology; Virtual screening

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIBIOTIC AGENT; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ANTIINFLAMMATORY AGENT; ANTIMALARIAL AGENT; ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT; AURISTATIN PE; BOROPHYCIN 11; CEMADOTIN; CRYPTOPHYCIN 1; CRYPTOPHYCIN 52; CURACIN A; CYANOVIRIN; CYANOVIRIN N; CYTOTOXIC AGENT; DOLASTATIN 10; DOLASTATIN 15; ENZYME INHIBITOR; HECTOCHLORIN; ILX 651; IMMUNOSUPPRESSIVE AGENT; JAMAICANAMIDE A; NATURAL PRODUCT; NON RIBOSOMAL PEPTIDE SYNTHASE; PEPTIDE SYNTHASE; POLYKETIDE SYNTHASE; SCYTONEMIN; SOBLIDOTIN; SYMPLOSTAIN 1; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; BIOTECHNOLOGY; CLINICAL TRIAL; COMPUTER PROGRAM; CYANOBACTERIUM; DATA BASE; DRUG RESEARCH; DRUG SCREENING; DRUG SYNTHESIS; DRUG TARGETING; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN TARGETING; PROTEOMICS; REVIEW; VIRTUAL REALITY;

EID: 48749122322     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.3.8.903     Document Type: Review

References (311)

1. Schopf JW, Packer BM. Early Archean (3.3-billion to 3.5-billion-year-old) microfossils from Warrawoona Group, Australia. Science 1987;237(4810):70-3
2. Sivonen, K, Halinen K, Sihvonen LM, et al. Bacterial diversity and function in the Baltic Sea with an emphasis on cyanobacteria. Ambio 2007;36(2-3):180-5
3. Anderson LK, Toole CM, A model for early events in the assembly pathway of cyanobacterial phycobilisomes. Molecular Microbiology 1998;30(3):467-474.
4. Lyons TW. Palaeoclimate: oxygen's rise reduced. Science 2007;448:1005-6
5. Codd GA, Edwards C, Beattle KA, et al. Fatal attraction to cyanobacteria? Nature 1992;359(6391):110-1
6. Krishnamurthy T, Carmichael WW, Sarver EW. Toxic peptides from freshwater cyanobacteria (blue-green algae). I. Isolation, purification and characterization of peptides from Microcystis aeruginosa and Anabaena flos-aquae. Toxicon 1986;24(9):865-73
7. Theiss WC, Carmichael WW, Wyman J, Bruner R. Blood pressure and hepatocellular effects of the cyclic heptapeptide toxin produced by the freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa strain PCC-7820. Toxicon 1988;26(7):603-13
8. Francis G. Poisonous Australian lake. Nature 1878;18:11-2
9. Carmichael WW, Bent PE. Hemagglutination method for detection of freshwater cyanobacteria (blue-green algae) toxins. Appl Environ Microbiol 1981;41(6):1383-8
10. Botes DP, Weasels PL, Kruger H, et al. Structural studies on cyanoginosins-LR,-YR,-YA, and-YM, peptide toxins from Microcystis aeruginosa. J Chem Soc Perkin Trans 1 1985;1985:2747-8
11. Fischer WJ, Dietrich DR. Pathological and biochemical characterization of microcystin-induced hepatopancreas and kidney damage in carp (Cyprinus carpio). Toxicol Appl Pharmacol 2000;164(1):73-81
12. Fischer WJ, Altheimer S, Cattori V, et al. Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol Appl Pharmacol 2005;203(3):257-63
13. Kujbida P, Hatanaka E, Campa A, et al. Analysis of chemokines and reactive oxygen species formation by rat and human neutrophils induced by microcystin-LA, -YR and -LR. Toxicon 2008;51(7):1274-80
14. Schrader KK, Dennis ME. Cyanobacteria and earthy/musty compounds found in commercial catfish (Ictalurus punctatus) ponds in the Mississippi Delta and Mississippi-Alabama Blackland Prairie. Water Res 2005;39(13):2807-14
15. Robin J, Cravedi JP, Hillenweck A, et al. Off flavor characterization and origin in French trout farming. Aquaculture 2006;260(1-4):128-38
16. Wiegand C, Pflugmacher S. Ecotoxicological effects of selected cyanobacterial secondary metabolites a short review. Toxicol Appl Pharmacol 2005;203(3):201-18
17. Davies-Coleman MT, Dzeha TM, Gray CA, et al. Isolation of homodolastatin 16, a new cyclic depsipeptide from a Kenyan collection of Lyngbya majuscula. J Nat Prod 2003;66(5):712-5
18. Simmons TL, Andrianasolo E, McPhail K, et al. Marine natural products as anticancer drugs. Mol Cancer Ther 2005;4(2):333-42
19. Fujiki H, Mori M, Nakayasu M, et al. Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters. Proc Natl Acad Sci USA 1981;78(6):3872-6
20. Nakayasu M, Fujiki H, Mori M, et al. Teleocidin, lyngbyatoxin A and their hydrogenated derivatives, possible tumor promoters, induce terminal differentiation in HL-60 cells. Cancer Lett 1981;12(4):271-7
21. Tan LT. Bioactive natural products from marine cyanobacteria for drug discovery. Phytochemistry 2007;68(7):954-79
22. Cruz-Rivera E, Paul V. Feeding by coral reef mesograzers: algae or cyanobacteria? Coral Reefs 2006;25(4):617-27
23. Eißler S, Stoncius A, Nahrwold M, Sewald N. The synthesis of cryptophycins. Synthesis 2006;(22):3747-89
24. Newman DJ, Cragg GM. Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod 2004;67(8):1216-38
25. Hildebrand M, Waggoner LE, Liu H, et al. bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina. Chem Biol 2004;11(11):1543-52
26. Williams AB, Jacobs RS. A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line. Cancer Lett 1993;71(1-3):97-102
27. Schmidt EW, Nelson JT, Rasko DA, et al. Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proc Natl Acad Sci USA 2005;102(20):7315-20
28. Hirose E, Maruyama T. What are the benefits in the ascidian - Prochloron symbiosis. Endocytobiosis Cell Res 2004;15:51-62
29. Available from: http://www.genomesonline.org
30. Williams PG, Moore RE, Paul VJ. Isolation and structure determination of lyngbyastatin 3, a lyngbyastatin 1 homologue from the marine cyanobacterium Lyngbya majuscula. Determination of the Configuration of the 4-amino-2,2-dimethyl-3-oxopentanoic acid unit in majusculamide C, dolastatin 12, lyngbyastatin 1, and lyngbyastatin 3 from Cyanobacteria. J Nat Prod 2003;66(10):1356-63
31. Moffitt MC, Louie GV, Bowman ME, et al. Discovery of two cyanobacterial phenylalanine ammonia lyases: kinetic and structural characterization. Biochemistry 2007;46(4):1004-12
32. Burja AM, Banaigs B, Abou-Mansour E, et al. Marine cyanobacteria - a prolific source of natural products. Tetrahedron 2001;57(46):9347-77
33. Hallam SE, Malpartida F, Hopwood DA. Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor. Gene 1988;74:305-20
34. Malpartida F, Hopwood DA. Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host. Biotechnology 1984;24:342-3
35. Barrios-Llerena ME, Burja AM, Wright PC. Genetic analysis of polyketide synthase and peptide synthetase genes in cyanobacteria as a mining tool for secondary metabolites. J Ind Microbiol Biotechnol 2007;34(6):443-56
36. Guyot M, Doreacute CJ, Devillers J. Typology of secondary cyanobacterial metabolites from minimum spanning tree analysis. SAR QSAR Environ Res 2004;15(2):101-14
37. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001;409(6822):860-921
38. Wolkenhauer O. 'Systems biology: the reincarnation of systems theory applied in biology?' Brief Bioinformatics 2001;2:258-70
39. Kitano H. Systems biology: a brief overview. Science 2002;295:1662-4
40. Gygi SP, Rochon Y, Franza BR, Aebersold R. Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 1999;19:1720-30
41. Anderson LSJ. A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 1997;18:533-7
42. Bothwell JHF, The long past of systems biology. New Phytologist 2006;170(1):6-10
43. Comprehensive Microbial Resource. Available from: http://cmr.tigr.org/ tigr-scripts/CMR/CmrHomePage.cgi
44. Sakharkar KR, Sakharkar MK, Chow VTK. A novel genomics approach for the identification of drug targets in pathogens, with special reference to pseudomonas aeruginosa. In Silico Biol 2004;4(3):355-60
45. Liu X, Huang W, Wu Q. Two-component signal transduction systems in the cyanobacterium synechocystis sp. PCC 6803. Tsinghua Sci Technol 2006;11(4):379-90
46. Alves-Rodrigues I, Galao RP, Meyerhans A, Diez J. Saccharomyces cerevisiae: a useful model host to study fundamental biology of viral replication. Virus Res 2006;120(1-2):49-56
47. Baumbach J, Wittkop T, Rademacher K, et al. CoryneRegNet 3.0-an interactive systems biology platform for the analysis of gene regulatory networks in corynebacteria and Escherichia coli. J Biotechnol 2007;129(2):279-89
48. Kriete A, Sokhansanj BA, Coppock DL, West GB. Systems approaches to the networks of aging. Ageing Res Rev 2006;5(4):434-48
49. Davidson EH. Genomic regulatory systems, in development and evolution. Academic Press: San Diego, CA; 2001
50. Davidov E, Holland J, Marple E, Naylor S. Advancing drug discovery through systems biology. Drug Discov Today 2003;8(4):175-83
51. Wise A, Gearing K, Rees S. Target validation of G-protein coupled receptors. Drug Discov Today 2002;7(4):235-46
52. Ramakrishnan L, Federspiel NA, Falkow S. Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family. Science 2000;288(5470):1436-9
53. Becker K, Bierbaum G, von Eiff C, et al. Understanding the physiology and adaptation of staphylococci: post-genomic approach. Int J Med Microbiol 2007;297(7-8):483-501
54. Josenhans C, Beier D, Linz B, et al. Pathogenomics of helicobacter. Int J Med Microbiol 2007;297(7-8):589-600
55. Burja AM, Dhamwichukorn S, Wright PC. Cyanobacterial postgenomic research and systems biology. Trends Biotechnol 2003;21(11):504-11
56. National Cancer database. [cited]. Available from: http://dtp.nci.nih.gov/docs/3d⊣tabase/dis3d.html
57. NCBI pubchem. [cited]. Available from: htrp://pubchem.ncbi.nlm.nih.gov/
58. ChemID Plus. [cited]. Available from: http://chem.sis.nlm.nih.gov/ chemidplus
59. Brahmachary M, Krishnan SPT, Koh JLY, et al. ANTIMIC: a database of antimicrobial sequences. Nucleic Acids Res 2004;32(Suppl 1):D586-9
60. Super Natural Database. [cited]. Available from: http://bioinformatics.charite.de/supernatural/
61. Salzberg SL, Deicher AL, Kasif S. Microbial gene identification using interpolated Markov models. Nucleic Acids Res 1998;26(2):544-8
62. Hayes WS, Borodovsky M. How to interpret an anonymous bacterial genome: machine learning approach to gene identification. Genome Res 1998;8(11):1154-71
63. Softberry. Available from: http://www.softberry.com/
64. Oliynyk M, Samborskyy M, Lester JB, et al. Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338. Nat Biotechnol 2007;25(4):447-53
65. Budde PP, Davis BM, Yuan J, Waldor MK. Characterization of a higBA toxin-antitoxin locus in Vibrio cholerae. J Bacteriol 2007;189(2):491-500
66. Wagschal K, Franqui-Villanueva D, Lee C, et al. Genetic and biochemical characterization of a novel bacterial A-L-Arabinofuranosidease. Enzyme Microb Technol 2007;40:747-53
67. Worley KC, Wiese BA, Smith RF. BEAUTY: an enhanced BLAST-based search tool that integrates multiple biological information resources into sequence similarity search results. Genome Res 1995;5(2):173-84
68. Krishnan A, Li K-B, Issac P. Rapid detection of conserved regions in protein sequences using wavelets. In Silico Biol 2004;4(0013)
69. Su QJ, Lu L, Saxonov S, Brutlag DL. eBLOCKs: enumerating conserved protein blocks to achieve maximal sensitivity and specificity. Nucleic Acids Res 2005;33(Suppl 1):D178-82
70. Yada T, Totoki Y, Takagi T, Nakai K. A novel bacterial gene-finding system with improved accuracy in locating start codons. DNA Res 2001;8:97-106
71. Bateman A, Birney E, Durbin R, et al. Pfam 3.1: 1313 multiple alignments and profile HMMs match the majority of proteins. Nucleic Acids Res 1999;27(1):260-2
72. Haft DH, Loftus BJ, Richardson DL, et al. TIGRFAMs: a protein family resource for the functional identification of proteins. Nucleic Acids Res 2001;29(1):41-3
73. Altschul SF, Koonin EM. Iterated profile searches with PSI-BLAST - a tool for discovery in protein databases. Trends Biochem Sci 1998;23(11):444-7
74. Tatusov RL, Koonin EM, Lipman DJ. A genomic perspective on protein families. Science 1997;278(5338):631-7
75. Winters-Hilt S. Hidden Markov model variants and their application. Feedback. BMC Bioinformatics 2006;7(Suppl 2):S14
76. Wang J, Leblanc É, Chang CF, et al. Pterin and folate reduction by the Leishmania tarentolae H locus short-chain dehydrogenase/reductase PTR1. Arch Biochem Biophys 1997;342(2):197-202
77. Azad AK, Sirakova TD, Fernandes ND, Kolattukudy PE. Gene knockout reveals a novel gene cluster for the synthesis of a class of cell wall lipids unique to pathogenic mycobacteria. J Biol Chem 1997;272(27):16741-5
78. Yao C, Donelson JE, Wilson ME. The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function. Mol Biochem Parasitol 2003;132(1):1-16
79. Houck KA, Kavlock RJ. Understanding mechanisms of toxicity: insights from drug discovery research. Toxicol Appl Pharmacol 2008;227(2):163-78
80. Dittmann E, Neilan BA, Borner T. Molecular biology of peptide and polyketide biosynthesis in cyanobacteria. Appl Microbiol Biotechnol 2001;57(4):467-73
81. Repka S, Koivula M, Harjunpa V, et al. Effects of phosphate and light on growth of and bioactive peptide production by the Cyanobacterium anabaena strain 90 and its anabaenopeptilide mutant. Appl Environ Microbiol 2004;70(8):4551-60
82. Lautru S, Challis GL. Substrate recognition by nonribosomal peptide synthetase multi-enzymes. Microbiology 2004;150(Pt 6):1629-36
83. Edwards DJ, Marques BL, Nogle LM, et al. Structure and biosynthesis of the Jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem Biol 2004;11(6):817-33
84. Schlegel I, Doan N, de Chazal N, Smith G. Antibiotic activity of new cyanobacterial isolates from Australia and Asia against green algae and cyanobacteria. J Appl Phycol 1998;10(5):471-9
85. Burns BP, Seifert A, Goh F, et al. Genetic potential for secondary metabolite production in stromatolite communities. FEMS Microbiol Lett 2005;243(1):293-301
86. Schembri MA, Neilan BA, Saint CP. Identification of genes implicated in toxin production in the cyanobacterium Cylindrospermopsis raciborskii. Environ Toxicol 2001;16(5):413-21
87. Neilan BA, Dittmann E, Rouhiainen L, et al. Nonribosomal peptide synthesis and toxigenicity of cyanobacteria. J Bacteriol 1999;181(13):4089-97
88. Luesch H, Chanda SK, Raya RM, et al. A functional genomics approach to the mode of action of apratoxin A. Nat Chem Biol 2006;2(3):158-67
89. Rachman H, Kaufmann SHE. Exploring functional genomics for the development of novel intervention strategies against tuberculosis. Int J Med Microbiol 2007;297(7-8):559-67
90. Palka-Santini M, Putzfeld S, Cleven BEE, et al. Rapid identification, virulence analysis and resistance profiling of Staphylococcus aureus by gene segment-based DNA microarrays: application to blood culture post-processing. J Microbiol Methods 2007;68(3):468-77
91. Hacker J, Blum-Oehler G, Muhldorfer I, Tschape H. Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution. Mol Microbiol 1997;23(6):1089-97
92. Galperin MY, Walker DR, Koonin EV. Analogous enzymes: independent inventions in enzyme evolution. Genome Res 1998;8(8):779-90
93. Federici L, Woebking B, Velamakanni S, et al. New structure model for the ATP-binding cassette multidrug transporter LmrA. Biochem Pharmacol 2007;74(5):672-8
94. Konings WN, Poelarends GJ. Bacterial multidrug resistance mediated by a homologue of the human multidrug transporter P-glycoprotein. IUBMB Life 2002;53(4-5):213-8
95. Peng X, Xu C, Ren H, et al. Proteomic analysis of the sarcosine-insoluble outer membrane fraction of Pseudomonas aeruginosa responding to ampicilin, kanamycin, and tetracycline resistance. J Proteome Res 2005;4(6):2257-65
96. Marahiel MA, Stachelhaus T, Mootz HD. Modular peptide synthetases involved in nonribosomal peptide synthesis. Chem Rev 1997;97(7):2651-73
97. Stachelhaus T, Mootz HD, Marahiel MA. The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases. Chem Biol 1999;6(8):493-505
98. Stachelhaus T, Huser A, Marahiel MA. Biochemical characterization of peptidyl carrier protein (PCP), the thiolation domain of multifunctional peptide synthetases. Chem Biol 1996;3(11):913-21
99. Stachelhaus T, Mootz HD, Bergendah V, Marahiel MA. Peptide bond formation in nonribosomal peptide biosynthesis: catalytic role of the condensation domain. J Biol Chem 1998;273(35):22773-81
100. Cane DE, Walsh CT. The parallel and convergent universes of polyketide synthases and nonribosomal peptide synthetases. Chem Biol 1999;6(12):319-25
101. Weber T, Marahiel MA. Exploring the domain structure of modular nonribosomal peptide synthetases. Structure 2001;9(1):R3-9
102. Kleinkauf H, Von Dohren H. A nonribosomal system of peptide biosynthesis. FEBS J 1996;236(2):335-51
103. Walsh CT, Chen H, Keating TA, et al. Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines. Curr Opin Chem Biol 2001;5(5):525-34
104. Rouhiainen L, Paulin L, Suomalainen S, et al. Genes encoding synthetases of cyclic depsipeptides, anabaenopeptilides, in Anabaena strain 90. Mol Microbiol 2000;37(1):156-67
105. Hoffmann D, Hevel JM, Moore RE, Moore BS. Sequence analysis and biochemical characterization of the nostopeptolide A biosynthetic gene cluster from Nostoc sp. GSV224. Gene 2003;311:171-80
106. Ramaswamy AM, Flatt PM, Edwards DJ, et al. The secondary metabolites and biosynthetic gene clusters of marine cyanobacteria. Applications in biotechnology. In: Proksch P, Muller WEG, editors, Frontiers in marine biotechnology. Horizon Bioscience; 2006. p. 175-224
107. Schwarzer D, Finking R, Marahiel MA. Nonribosomal peptides: from genes to products. Nat Prod Rep 2003;20(3):275-87
108. Ishida K, Christiansen G, Yoshida WY, et al. Biosynthesis and structure of aeruginoside 126A and 126B, cyanobacterial peptide glycosides bearing a 2-carboxy-6-hydroxyoctahydroindole moiety. Chem Biol 2007;14(5):565-76
109. Hopwood DA, Sherman DH. Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Ann Rev Genet 1990;24:37-66
110. Hopwood DA. Genetic contributions to understanding polyketide synthases. Chem Rev 1997;97(7):2465-97
111. Fischbach MA, Walsh CT. Directing biosynthesis. Science 2006;314(5799):603-5
112. Weissman KJ, Leadlay PF. Combinatorial biosynthesis of reduced polyketides. Nat Rev Microbiol 2005;3(12):925-36
113. Welker M, Von Dohren H. Cyanobacterial peptides - nature's own combinatorial biosynthesis. FEMS Microbiol Rev 2006;30(4):530-63
114. Pfeifer BA, Khosla C. Biosynthesis of polyketides in heterologous hosts. Microbiol Mol Biol Rev 2001;65(1):106-18
115. Khosla C. Natural product biosynthesis: a new interface between enzymology and medicine. J Org Chem 2000;65(24):8127-33
116. Schwarzer D, Marahiel MA. Multimodular biocatalysts for natural product assembly. Naturwissenschaften 2001;88(3):93-101
117. Salomon CE, Magarvey NA, Sherman DH. Merging the potential of microbial genetics with biological and chemical diversity: an even brighter future for marine natural product drug discovery. Nat Prod Rep 2004;21(1):105-21
118. Freiberg C, Brotz-Oesterhelt H, Labischinski H. The impact of transcriptome and proteome analyses on antibiotic drug discovery. Curr Opin Microbiol 2004;7(5):451-9
119. Picollet-D'hahan N, Sauter F, Ricoul F, et al. Multi-patch: a chip-based ion-channel assay system for drug screening in Proceedings of ICMENS2003. The 2003 International Conference on MEMS, NANO and Smart Systems. 2003. Banff, Alberta - Canada
120. Ross DT, Scherf U, Eisen MB, et al. Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet 2000;24(3):227-35
121. Hamadeh HK, Bushel PR, Jayadev S, et al. Prediction of compound signature using high density gene expression profiling. Toxicol Sci 2002;67(2):232-40
122. Hamadeh HK, Bushel PR, Jayadev S, et al. Gene expression analysis reveals chemical-specific profiles. Toxicol Sci 2002;67(2):219-31
123. Ishige T, Krause M, Bott M, Wendisch VF, Sahm H. The phosphate starvation stimulon of Corynebacterium glutamicum determined by DNA microarray analyses. J Bacteriol 2003;185(15):4519-29
124. Minagawa S, Ogasawara H, Kato A, et al. Identification and molecular characterization of the Mg2+ stimulon of Escherichia coli. J Bacteriol 2003;185(13):3696-702
125. Gillis B, Gavin IM, Arbieva Z, et al. Identification of human cell responses to benzene and benzene metabolites. Genomics 2007;90(3):324-33
126. Hihara Y, Kamei A, Kanehisa M, et al. DNA microarray analysis of cyanobacterial gene expression during acclimation to high light. Plant Cell 2001;13(4):793-806
127. Zheng M, Wang X, Templeton LJ, et al. DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide. J Bacteriol 2001;183(15):4562-70
128. Weinrick B, Dunman PM, McAleese F, et al. Effect of mild acid on gene expression in Staphylococcus aureus. J Bacteriol 2004;186(24):8407-23
129. Baichoo N, Wang T, Ye R, Helmann JD. Global analysis of the Bacillus subtilis fur regulon and the iron starvation stimulon. Mol Microbiol 2002;45(6):1613-29
130. Pullan ST, Gidley MD, Jones RA, et al. Nitric oxide in chemostat-cultured Escherichia coli is sensed by Fnr and other global regulators: Unaltered methionine biosynthesis indicates lack of S nitrosation. J Bacteriol 2007;189(5):1845-55
131. Elnitski L, Jin VX, Farnham PJ, Jones SJM. Locating mammalian transcription factor binding sites: a survey of computational and experimental techniques. Genome Res 2006;16(12):1455-64
132. Rhodius VA, LaRossa RA. Uses and pitfalls of microarrays for studying transcriptional regulation. Curr Opin Microbiol 2003;6(2):114-9
133. Freiberg C, Brunner NA. Genome-wide mRNA profiling:impact on compound evaluation and target identification in anti-bacterial research. Drug Discov Today Targets 2002;1(1):20-9
134. Alper HG. Stephanopoulos, Global transcription machinery engineering: a new approach for improving cellular phenotype. Metab Eng 2007;9(3):258-67
135. Brötz-Oesterhelt H, Elisabeth J, Labischinski BH. Bacterial proteomics and its role in antibacterial drug discovery. Mass Spectrom Rev 2005;24(4):549-65
136. Witze ES, Old WM, Resing KA, Ahn NG. Mapping protein post-translational modifications with mass spectrometry. Nat Methods 2007;4(10):798-806
137. Lee KH. Proteomics: a technology driven and technology-limited discovery science. Trends Biotechnol 2001;19:217-22
138. Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature 2003;422:198-207
139. Gygi SP, Rist B, Gerber SA, et al. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 1999;17:994-9
140. Ross PL, Huang YN, Marchese JN, et al. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 2004;3(12):1154-69
141. Applied Biosystems, et al. [cited]. Available from: http://www3.appliedbiosystems.com/cms/groups/psm_marketing/documents/ generaldocuments/cms_042787.pdf
142. Williamson BL, Ross PL, Pillai S, et al. Protein quantitation using a novel 8-plex set of isobaric peptide labels. In: HUP O 5th Annual World Congress. 28 Oct - 1 Nov 2006; Long Beach, CA
143. Choe L, D'Ascenzo M, Relkin NR, et al. 8-plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer's disease. Proteomics 2007;7(20):3651-60
144. Ow SY, Stensjö K, Lindblad P, Wright P. An 8-plex iTRAQ shotgun proteomics investigation of N2-fixing heterocysts in the Cyanobacterium nostoc sp. PCC 7120. In: 55th ASMS Conference on Mass Spectrometry Indianapolis; USA
145. Chong PK, Gan CS, Pham TK, Wright PC.. Isobaric tags for relative and absolute quantitation (iTRAQ) reproducibility: implication of multiple injections. J Proteome Res 2006;5(5):1232-40
146. Gan CS, Chong PK, Pham TK, Wright PC. Technical, experimental, and biological variations in isobaric tags for relative and absolute quantitation (iTRAQ). J Proteome Res 2006;6:821-7
147. Choe LH, Aggarwal K, Franck Z, Lee KH. A comparison of the consistency of proteome quantitation using two-dimensional electrophoresis and shotgun isobaric tagging in Escherichia coli cells. Electrophoresis 2005;26(12):2437-49
148. Lueking A, Horn M, Eickhoff H, et al. Protein microarrays for gene expression and antibody screening. Anal Biochem 1999;270:103-11
149. Fang Y, Lahiri J, Picard L. G protein-coupled receptor microarrays for drug discovery. Drug Discov Today 2003;8(16):755-61
150. Fiehn O. Metabolomics - the link between genotypes and phenotypes. Plant Mol Biol 2002;48:155-71
151. ChemSpider. [cited]. Available from: http://www.chemspider.com/ Search.aspx
152. EBI Macromolecular Structure Database Group [cited]. Available from: http://www.ebi.ac.uk/msd/
153. NIAID. [cited]. Available from: http://chemdb.niaid.nih.gov/ struct_search/an/an_search.htm
154. MATADOR. [cited 27 Nov 2007]. Available from: http://matador.embl.de/
155. Drug Bank. [cited]. Available from: http://redpoll.pharmacy.ualberta.ca/ drugbank/
156. Super Targets. [cited]. Available from: http://insilico.charite.de/ supertarget/main.html#Home
157. LifeSpan Drug Target. [cited]. Available from: http://www.lsbio.com/ products/expression/DrugTargetDB.aspx
158. Li H, Gao Z, Kang L, et al. TarFisDock: a web server for identifying drug targets with docking approach. Nucleic Acids Res 2006;34(Suppl 2):W219-24. Available from: http://www.dddc.ac.cn/tarfisdock/index.php
159. Wheeler DL, Barrett T, Benson DA, et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2005;33(Database Issue)
160. Drews J. Drug discovery: a historical perspective. Science 2000;287(5460):1960-4
161. Debouck C, Metcalf B. The impact of genomics on drug discovery. Ann Rev Pharmacol Toxicol 2000;40(1):193-208
162. Walters WP, Stahl MT, Murcko MA. Virtual screening - an overview. Drug Discov Today 1998;3(4):160-78
163. Waszkowycz B, Perkins TDJ, Sykes RA, Li J. Large-scale virtual screening for discovering leads in the postgenomic era. IBM Syst J 2001;40(2):360-76
164. Singh SS. Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Curr Drug Metab 2006;7(2):165-82
165. Marchetti S, Schellens JHM. The impact of FDA and EMEA guidelines on drug development in relation to Phase 0 trials. Br J Cancer 2007;97(5):577-81
166. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46(1-3):3-26
167. Wolber G, Seidel T, Bendix F, Langer T. Molecule-pharmacophore superpositioning and pattern matching in computational drug design. Drug Discov Today In press
168. Langer T, Hoffmann RD. Pharmacophores and pharmacophore searches. In: Mannhold R, Kubinyi H, Folkers G, editors. Methods and Principles in Medicinal Chemistry. Wiley-VCH: Chichester, UK; 2006
169. Langer T, Hoffmann RD. Pharmacophores and pharmacophore searches. Wiley-VCH; 2006
170. Catalyst. Accelrys AI. [cited November 2007]. Available from: www.accelrys.com [Retrived on November 2007]
171. Phase SI. [cited]. Available from: www.schrodinger.com [Retrieved on November 2007]
172. MOE (Molecular Operating Environment), C.C.G. [cited]. Available from: www.chemcomp.com [Retrieved on November 2007]
173. Gerhard Wolber RK. Pharmacophores from macromolecular complexes with ligandscout. In: DRDH Thierry Langer, editor, Pharmacophores and pharmacophore searches; 2006. p. 131-50
174. Webpage. Large-scale virtual screening for discovering leads in the postgenomic era. 2001 [cited 23/10/2007]. Available from: http://www.research.ibm.com/journal/sj/402/waszkowycz.html
175. Cambridge Structure Database. [cited]. Available from: http://www.ccdc.cam.ac.uk/products/csd/
176. Rognan D. Chemogenomic approaches to rational drug design. Br J Pharmacol 2007;152:38-52
177. Stockwell BR. Chemical genetics: ligand-based discovery of gene function. Nat Rev Genet 2000;1(2):116-25
178. Protein Database. Available from: www.pdb.org
179. Dawson RJ, Locher KP. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett 2007;581(5):935-8
180. Sanches M, Krauchenco S, Martins NH et al. Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development. J Mol Biol 2007;369(4):1029-40
181. Cummings MD, Schubert C, Parks DJ, et al. Substituted 1,4-benzodiazepine-2,5-diones as 3B1;-helix mimetic antagonists of the HDM2-p53 protein-protein interaction. Chem Biol Drug Des 2006;67(3):201-5
182. Tovchigrechko A, Vakser IA. GRAMM-X public web server for protein-protein docking. Nucleic Acids Res 2006;34(Suppl 2):W310-4
183. Target DB. Available from: http://targetdb.pdb.org/
184. Hu L, Benson MLL, Smith RD, et al. Binding MOAD (Mother Of All Databases). Proteins: Structure, Function, and Bioinformatics 2005;60(3):333-40
185. Corina. [cited]. Available from: www.molecular-networks.com/online_demos/ corina_demo.html
186. Pettersen EF, Goddard TD, Huang CC, et al. UCSF chimera - a visualization system for exploratory research and analysis. J Comput Chem 2004;25(13):1605-12
187. Stevenson CS, Capper EA, Roshak AK, et al. The identification and characterization of the marine natural product scytonemin as a novel antiproliferative pharmacophore. J Pharmacol Exp Ther 2002;303(2):858-66
188. Proteau PJ, Gerwick WH, Garcia-Pichel F, Castenholz R. The structure of scytonemin, an ultraviolet sunscreen pigment from the sheaths of cyanobacteria. Experientia 1993;49(9):825-9
189. Li Q, Lai L. Prediction of potential drug targets based on simple sequence properties. BMC Bioinformatics 2007;8(1):353
190. Jones G, Willett P, Glen RC, et al. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 1997;267(3):727-48
191. CCDC/Astex validation data set. Available from: http://www.ccdc.cam.ac.uk/
192. Chiocchini C, Linne U, Stachelhaus T. In vivo biocombinatorial synthesis of lipopeptides by COM domain-mediated reprogramming of the surfactin biosynthetic complex. Chem Biol 2006;13(8):899-908
193. Gerwick WH, Tong Tan L, Sitachitta N. Nitrogen-containing metabolites from marine cyanobacteria, in alkaloids. Chem Biol 2001:75-184
194. Moore RE, Corbett TH, Patterson GML, Valeriote FA. The search for new antitumor drugs from blue-green algae. Curr Pharm Des 1996;2(3):317-30
195. Sessa C, Weigang-Kohler K, Pagani O, et al. Phase I and pharmacological studies of the cryptophycin analogue LY355703 administered on a single intermittent or weekly schedule. Eur J Cancer 2002;38(18):2388-96
196. Boyd MR, Gustafson KR, McMahon JB, et al. Discovery of cyanovirin-N, a novel human immunodeficiency virus- inactivating protein that binds viral surface envelope glycoprotein gp120:otential applications to microbicide development. Antimicrob Agents Chemother 1997;41(7):1521-30
197. Available from: http://www.aidsinfo.nih.gov
198. Burja AM, Abou-Mansour E, Banaigs B, et al. Culture of the marine cyanobacterium, Lyngbya majuscula (Oscillatoriaceae), for bioprocess intensified production of cyclic and linear lipopeptides. J Microbiol Methods 2002;48(2-3):207-19
199. Haefner B. Drugs from the deep: marine natural products as drug candidates. Drug Discov Today 2003;8(12):536-44
200. Dembitsky VM, Srebnik M. Natural halogenated fatty acids: their analogues and derivatives. Prog Lipid Res 2002;41(4):315-67
201. Walsh CT. Polyketide and nonribosomal peptide antibiotics: modularity and versatility. Science 2004;303(5665):1805-10
202. Donadio S, Sosio M. Strategies for combinatorial biosynthesis with modular polyketide synthases. Comb Chem High Throughput Screen 2003;6(6):489-500
203. Heinemann M, Panke S. Synthetic biology - putting engineering into biology. Bioinformatics 2006;22(22):2790-9
204. Available from: http://parts.mit.edu/registry/index.php/Main_Page
205. Zhou X, Cai S, Hong A, et al. Microfluidic PicoArray synthesis of oligodeoxynucleotides and simultaneous assembling of multiple DNA sequences. Nucleic Acids Res 2004;32(18):5409-17
206. Peiru S, Menzella HG, Rodriguez E, et al. Production of the potent antibacterial polyketide erythromycin C in Escherichia coli. Appl Environ Microbiol 2005;71(5):2539-47
207. Ro D-K, Paradise EM, Ouellet M, et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 2006;440(7086):940-3
208. Khosla C, Keasling JD. Metabolic engineering for drug discovery and development. Nat Rev Drug Discov 2003;2(12):1019-25
209. Martin VJJ, Pitera DJ, Withers ST, et al. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat Biotech 2003;21(7):796-802
210. Freitag A, Mendez C, Salas JA, et al. Metabolic engineering of the heterologous production of clorobiocin derivatives and elloramycin in Streptomyces coelicolor M512. Metab Eng 2006;8(6):653-61
211. Li R, Townsend CA. Rational strain improvement for enhanced clavulanic acid production by genetic engineering of the glycolytic pathway in Streptomyces clavuligerus. Metab Eng 2006;8(3):240-52
212. Gould SJ, Minott DA. Biosynthesis of caperomycin. 1. Incorporation of arginine. J Org Chem 1992;57:5214-7
213. Hutchinson CR, Fujii I. Polyketide synthase gene manipulation: a structure-function approach in engineering novel antibiotics. Ann Rev Microbiol 1995;49(1):201-38
214. Staunton J, Weissman KJ. Polyketide biosynthesis: a millennium review. Nat Prod Rep 2001;18(4):380-416
215. Katz L, McDaniel R. Novel macrolides through genetic engineering. Med Res Rev 1999;19(6):543-58
216. Khosla C. Natural product biosynthesis: a new interface between enzymology and medicine. J Org Chem 2000;65(24):8127-33
217. Schwecke T, Aparicio JF, Molnar I, et al. The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc Natl Acad Sci USA 1995;92(17):7839-43
218. Stachelhaus T, Schneider A, Marahiel MA. Rational design of peptide antibiotics by targeted replacement of bacterial and fungal domains. Science 1995;269(5220):69-72
219. Finking R, Marahiel MA. Biosynthesis of nonribosomal peptides. Ann Rev Microbiol 2004;58:453-88
220. Sieber SA, Marahiel MA. Molecular mechanisms underlying nonribosomal peptide synthesis: Approaches to new antibiotics. Chem Rev 2005;105(2):715-38
221. Available from: http://linux1.nii.res.in/-pksdb/polyketide.html and references therein
222. Luu HA, Chen DZX, Magoon J, et al. Quantification of diarrhetic shellfish toxins and identification of novel protein phosphatase inhibitors in marine phytoplankton and mussels. Toxicon 1993;31(1):75-83
223. Moore RE. Cyclic peptides and depsipeptides from cyanobacteria: a review. J Ind Microbiol 1996;16(2):134-43
224. Welker M, Brunke M, Preussel K, et al. Diversity and distribution of Microcystis (Cyanobacteria) oligopeptide chemotypes from natural communities studied by single-colony mass spectrometry. Microbiology 2004;150(Pt 6):1785-96
225. Chun HG, Davies B, Hoth D, Didemnin B. The first marine compound entering clinical trials as an antineoplastic agent. Invest New Drugs 1986;4(3):279-84
226. Sakai R, Rinehart KL, Kishore V, et al. Structure-activity relationships of the didemnins. J Med Chem 1996;39(14):2819-34
227. Rinehart KL. Antiviral agents from novel marine and terrestrial sources. Adv Exp Med Biol 1992;312:41-60
228. Rinehart KL, Kishore V, Bible KC, et al. Didemnins and tunichlorin: novel natural products from the marine tunicate Trididemnum solidum. J Nat Prod 1988;51(1):1-21
229. Mitchell SS, Faulkner DJ, Rubins K, Bushman FD. Dolastatin 3 and two novel cyclic peptides from a palauan collection of Lyngbya majuscula. Nat Prod 2000;63(2):279-82
230. Milligan KE, Marquez BL, Williamson RT, Gerwick WH. Lyngbyabellin B, a toxic and antifungal secondary metabolite from the marine cyanobacterium Lyngbya mojuscula. J Nat Prod 2000;63(10):1440-3
231. Singh IP, Milligan KE, Gerwick WH. Tanikolide, a toxic and antifungal lactone from the marine cyanobacterium Lyngbya majuscula. J Nat Prod 1999;62(9):1333-5
232. Márquez, B, Verdier-Pinard P, Hamel E, Gerwick WH. Curacin D, an antimitotic agent from the marine cyanobacterium Lyngbya majuscula. Phytochemistry 1998;49(8):2387-9
233. Ohta S, Ono F, Shiomi Y, et al. Anti-herpes simplex virus substances produced by the marine green alga, Dunaliella primolecta. J Appl Phycol 1998;10(4):349-55
234. Zhang LH, Longley RE, Koehn FE. Antiproliferative and immunosuppressive properties of microcolin A, a marine-derived lipopeptide. Life Sci 1997;60(10):751-62
235. Endo Y, Ohno M, Hirano M, et al. Teleocidins and benzolactams inhibit cell killing by human immunodeficiency virus type 1 (HIV-1). Biol Pharm Bull 1994;17(8):1147-9
236. Beutler JA, Alvarado AB, Schaufelberger DE, et al. Dereplication of phorbol bioactives: Lyngbya majuscula and Croton cuneatus. J Nat Prod 1990;53(4):867-74
237. Aimi N, Odaka H, Sakai SI, et al. Lyngbyatoxins B and C, two new irritants from Lyngbya majuscula. J Nat Prod 1990;53(6):1593-6
238. Cruz-Rivera E, Paul VJ. Chemical deterrence of a cyanobacterial metabolite against generalized and specialized grazers. J Chem Ecol 2007;33(1):213-7
239. Bunyajetpong S, Yoshida WY, Sitachitta N, Kaya K. Trungapeptins A-C, cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. J Nat Prod 2006;69(11):1539-42
240. Al-Shehri AM. Factors affecting alkaline phosphatase activity of the marine cyanobacterium Lyngbya majuscula. J Biol Sci 2006;6(5):931-5
241. Han B, Gross H, Goeger DE, et al. Aurilides B and C, cancer cell toxins from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. J Nat Prod 2006;69(4):572-5
242. LePage KT, Goeger D, Yokokawa F, et al. The neurotoxic lipopeptide kalkitoxin interacts with voltage-sensitive sodium channels in cerebellar granule neurons. Toxicol Lett 2005;158(2):133-9
243. Chang Z, Sitachitta N, Rossi JV, et al. Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula. J Nat Prod 2004;67(8):1356-67
244. White JD, Xu Q, Lee CS, Valeriote FA. Total synthesis and biological evaluation of (+)-kalkitoxin, a cytotoxic metabolite of the cyanobacterium Lyngbya majuscula. Org Biomol Chem 2004;2(14):2092-102
245. Ennis SC, Cumpstey I, Fairbanks AJ, et al. Total syntheses of lyngbyabellins A and B, potent cytotoxic lipopeptides from the marine cyanobacterium Lyngbya majuscula. Tetrahedron 2002;58(46):9445-58
246. Muir JC, Pattenden G, Ye T. Total synthesis of (+)-curacin A, a novel antimitotic metabolite from a cyanobacterium. J Chem Soc Perkin Trans 1 2002;(20):2243-50
247. MacMillan JB, Molinski TF. Caylobolide A, a unique 36-membered macrolactone from a bahamian Lyngbya majuscula. Org Lett 2002;4(9):1535-8
248. Nogle LM, Gerwick WH. Somocystinamide A, a novel cytotoxic disulfide dimer from a fijian marine cyanobacterial mixed assemblage. Org Lett 2002;4(7):1095-8
249. Marquez BL, Watts KS, Yokochi A, et al. Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly. J Nat Prod 2002;65(6):866-71
250. Luesch H, Pangilinan R, Yoshida WY, et al. Pitipeptolides A and B, new cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. J Nat Prod 2001;64(3):304-7
251. Gustafson KR, Cardellina II JH, Fuller RW, et al. AIDS-antiviral sulfolipids from cyanobacteria (blue-green algae). J Natl Cancer Inst 1989;81(16):1254-8
252. Barchi JJ Jr, Moore RE, Patterson GML. Acutiphycin and 20,21-didehydroacutiphycin, new antineoplastic agents from the cyanophyte Oscillatoria acutissima. J Am Chem Soc 1984;106(26):8193-7
253. Reshef V, Mizrachi E, Maretzki T, et al. New acylated sulfoglycolipids and digalactolipids and related known glycolipids from cyanobacteria with a potential to inhibit the reverse transcriptase of HIV-1. J Nat Prod 1997;60(12):1251-60
254. Hayashi O, Ono S, Ishii K, et al. Enhancement of proliferation and differentiation in bone marrow hematopoietic cells by Spirulina (Arthrospira) platensis in mice. J Appl Phycol 2006;18(1):47-56
255. Ayehunie S, Belay A, Baba TW, Ruprecht RM. Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis). J Acquir Immune Defic Syndr 1998;18(1):7-12
256. Bhat VB, Madyastha KM. C-Phycocyanin: a potent peroxyl radical scavenger in vivo and in vitro. Biochem Biophys Res Commun 2000;275(1):20-5
257. Patel A, Mishra S, Ghosh PK. Antioxidant potential of C-phycocyanin isolated from cyanobacterial species Lyngbya, Phormidium and Spirulina spp. Indian J Biochem Biophys 2006;43(1):25-31
258. Onodera H, Oshima Y, Henriksen P, Yasumoto T. Confirmation of anatoxin-a(s), in the cyanobacterium Anabaena lemmermannii, as the cause of bird kills in Danish lakes. Toxicon 1997;35(11):1645-8
259. Bumke-Vogt C, Mailahn W, Rotard W, Chorus I. A highly sensitive analytical method for the neurotoxin anatoxin-a, using GC-ECD, and first application to laboratory cultures. Phycologia 1996;35(Suppl):51-6
260. Matsunaga S, Moore RE, Niemczura WP, Carmichael WW. Anatoxin-a(s), a potent anticholinesterase from Anabaena flos-aquae. J Am Chem Soc 1989;111(20):8021-3
261. Stratmann K, Belli J, Jensen CM, et al. Aulosirazole, a novel solid tumor selective cytotoxin from the blue-green alga Aulosira fertilissima. J Org Chem 1994;59(21):6279-81
262. Bernardo PH, Chai CLL, Heath GA, et al. Synthesis, electrochemistry, and bioactivity of the cyanobacterial calothrixins and related quinones. J Med Chem 2004;47(20):4958-63
263. Moore BS, Chen JL, Patterson GML, et al. Paracyclophanes from blue-green algae. J Am Chem Soc 1990;112(10):4061-3
264. Saker ML, Eaglesham GK. The accumulation of cylindrospermopsin from the cyanobacterium Cylindrospermopsis raciborskii in tissues of the Redclaw crayfish Cherax quadricarinatus. Toxicon 1999;37(7):1065-77
265. Carmichael WW, Eschedor JT, Patterson GM, Moore RE. Toxicity and partial structure of a hepatotoxic peptide produced by the cyanobacterium Nodularia spumigena Mertens emend. L575 from New Zealand. Appl Environ Microbiol 1988;54(9):2257-63
266. Honkanen RE, Dukelow M, Zwiller J, et al. Cyanobacterial nodularin is a potent inhibitor of type 1 and type 2A protein phosphatases. Mol Pharmacol 1991;40(4):577-83
267. Lehtimaki J, Lyra C, Suomalainen S, et al. Characterization of Nodularia strains, cyanobacteria from brackish waters, by genotypic and phenotypic methods. Int J Syst Evol Microbiol 2000;50(Pt 3):1043-53
268. Moore RE, Bornemann V, Niemczura WP, et al. Puwainaphycin C, a cardioactive cyclic peptide from the blue-green alga Anabaena BQ-16-1. Use of two-dimensional 13C-13C and 13C-15N correlation spectroscopy in sequencing the amino acid units. J Am Chem Soc 1989;111(16):6128-32
269. Yang X, Shimizu Y, Steiner JR, Clardy J. Nostoclide I and II, extracellular metabolites from a symbiotic cyanobacterium, Nostoc sp., from the lichen Peltigera canina. Tetrahedron Lett 1993;34(5):761-4
270. Bohm GA, Pfleiderer W, Boger P, Scherer S. Structure of a novel oligosaccharide-mycosporine-amino acid ultraviolet A/B sunscreen pigment from the terrestrial cyanobacterium Nostoc commune. J Biol Chem 1995;270(15):8536-9
271. Jaki B, Orjala J, Heilmann J, et al. Novel extracellular diterpenoids with biological activity from the cyanobacterium Nostoc commune. J Nat Prod 2000;63(3):339-43
272. Dey B, Lerner DL, Lusso P, et al. Multiple antiviral activities of cyanovirin-N: blocking of human immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and inhibition of diverse enveloped viruses. J Virol 2000;74(10):4562-9
273. Easer MT, Mori T, Mondor I, et al. Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120. J Virol 1999;73(5):4360-71
274. Stewart JB, Bornemann V, Lu Chen J, et al. Cytotoxic, fungicidal nucleosides from blue green algae belonging to the scytonemataceae. J Antibiot 1988;41(8):1048-56
275. Moore RE, Patterson GML, Mynderse JS, et al. Furusawa toxins from cyanophytes belonging to the scytonemataceae. Pure Appl Chem 1986;58:263-71
276. Rouhiainen L, Vakkilainen T, Siemer BL, Buikema W, Haselkorn R, Sivonen K. Genes coding for hepatotoxic heptapeptides (microcystins) in the cyanobacterium Anabaena strain 90. Appl Environ Microbiol 2004;70(2):686-92
277. Chang Z, Flatt P, Gerwick WH, et al. 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 2002;296(1-2):235-47
278. Chang Z, Sitachitta N, Rossi JV, et al. Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula. J Nat Prod 2004;67(8):1356-67
279. Edwards DJ, Gerwick WH. Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase. J Am Chem Soc 2004;126(37):11432-3
280. Tillett D, Dittmann E, Erhard M, et al. Structural organization of microcystin biosynthesis in Microcystis aetuginosa PCC7806: an integrated peptide-polyketide synthetase system. Chem Biol 2000;7(10):753-64
281. Nishizawa T, Asayama M, Fujii K, et al. Genetic analysis of the peptide synthetase genes for a cyclic heptapeptide microcystin in Microcystis spp. J Biochem (Tokyo) 1999;126(3):520-9
282. Christiansen G, Fastner J, Erhard M, et al. Microcystin biosynthesis in planktothrix: genes, evolution, and manipulation. J Bacteriol 2003;185(2):564-72
283. Becker JE, Moore RE, Moore BS. Cloning, sequencing, and biochemical characterization of the nostocyclopeptide biosynthetic gene cluster: molecular basis for imine macrocyclization. Gene 2004;325:35-42
284. Hess Lab. Available from: http://www.cyanolab.de/
285. Pakrasi Lab. Available from: http://sysbio.wustl.edu/pakrasi/
286. Ferran Garcia-Pichel's Lab. Available from: http://www.public.asu.edu/ -ferran/
287. Susan Golden Lab. Available from: http://www.bio.tamu.edu/FACMENU/ FACULTY/GoldenS.htm
288. Hans Matthijs. Available from: http://staff.science.uva.nl/-hansmatt/
289. Wright's Lab. Available from: http://shef.ac.uk/besg
290. Rakefet Schwarz. Available from: http://www.biu.ac.il/faculty/schwarr2/
291. The Dismukes Group (and BiosolarH2 consortium). Available from: http://www.princeton.edu/-catalase/
292. Vermass Lab. Available from: http://photoscience.la.asu.edu/photosyn/ faculty/vermaas.html
293. Church Lab. Available from: http://arep.med.harvard.edu/
294. Horgen FD, Kazmierski EB, Westenburg HE, et al. Malevamide D: Isolation and structure determination of an isodolastatin H analogue from the marine cyanobacterium Symploca hydnoides. J Nat Prod 2002;65(4):487-91
295. Luesch H, et al. Symplostatin 3, a new dolastatin 10 analogue from the marine cyanobacterium Symploca sp. VP452. J Nat Prod 2002;65(1):16-20
296. Luesch H, Yoshida WY, Moore RE, et al. The cyanobacterial origin of potent anticancer agents originally isolated from sea hares. Curr Med Chem 2002;9(20):1791-806
297. Natsume T, Watanabe JI, Tamaoki S, et al. Characterization of the interaction of TZT-1027, a potent antitumor agent, with tubulin. Jpn J Cancer Res 2000;91(7):737-47
298. Kobayashi M, Natsume T, Tamaoki S, et al. Antitumour activity of TZT-1027, a novel Dolastatin 10 derivative. Jpn J Cancer Res 1997;88(3):316-27
299. Sato M, Sagawa M, Nakazato T, et al. A natural peptide, dolastatin 15, induces G2/M cell cycle arrest and apoptosis of human multiple myeloma cells. Int J Oncol 2007;30(6):1453-9
300. Hu MK, Huang WS. Synthesis and cytostatic properties of structure-simplified analogs of dolastatin 15. J Peptide Res 1999;54(6):460-7
301. Ebbinghaus S, Rabin E, Hersh E, et al. A phase I study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously daily for 5 consecutive days every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 2005;11(21):7807-16
302. Harrigan GG, Luesch H, Yoshida WY, et al. Symplostatin 2: a dolastatin 13 analogue from the marine cyanobacterium Symploca hydnoides. J Nat Prod 1999;62(4):655-8
303. Harrigan GG, Luesch H, Yoshida WY, et al. Symplostatin 1: a dolastatin 10 analogue from the marine cyanobacterium Symploca hydnoides. J Nat Prod 1998;61(9):1075-7
304. Verdier-Pinard P, Lai JY, Yoo HD, et al. Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells. Mol Pharmacol 1998;53(1):62-76
305. Orjala J, Nagle DG, Hsu VL, Gerwick WH. Antillatoxin: an exceptionally ichthyotoxic cyclic lipopeptide from the tropical cyanobacterium Lyngbya majuscula. J Am Chem Soc 1995;117(31):8281-2
306. Yokokawa F, Fujiwara H, Shioiri T. Total synthesis and revision of absolute stereochemistry of antillatoxin, an ichthyotoxic cyclic lipopeptide from marine cyanobacterium Lyngbya majuscula. Tetrahedron 2000;56(12):1759-75
307. LePage KT, Goeger D, Yokokawa F, et al. The neurotoxic lipopeptide kalkitoxin interacts with voltage-sensitive sodium channels in cerebellar granule neurons. Toxicol Lett 2005;158(2):133-9
308. Luesch H, Chanda SK, Rays RM, et al. A functional genomics approach to the mode of action of apratoxin A. Nat Chem Biol 2006;2(3):158-67
309. Orjala J, Gerwick WH. Barbamide, a chlorinated metabolite with molluscicidal activity from the Caribbean cyanobacterium Lyngbya majuscula. J Nat Prod 1996;59(4):427-30
310. Tokuda H, Nishino H, Shirahashi H, et al. Inhibition of 12-O-tetradecanoylphorbol-13-acetate promoted mouse skin papilloma by digalactosyl diacylglycerols from the fresh water cyanobacterium Phormidium tenue. Cancer Lett 1996;104(1):91-5
311. Shirahashi H, Murakami N, Watanabe M, et al. Isolation and identification of anti-tumor-promoting principles from the fresh-water cyanobacterium Phormidium tenue. Chem Pharm Bull (Tokyo) 1993;41(9):1664-6