Considerations of the chemical biology of microbial natural products provide an effective drug discovery strategy

Archives of Pharmacal Research

Volumn 38, Issue 9, 2015, Pages 1591-1605

  Choi, Hyukjae ^a   Oh, Dong Chan ^b  

^a Yeungnam University   (South Korea)

^b Seoul National University   (South Korea)

Author keywords

Bioactive compound; Chemical biology; Drug discovery; Insect; Marine invertebrate; Microbe; Natural product; Symbiosis

Indexed keywords

ANTIBIOTIC AGENT; NATURAL PRODUCT; NEW DRUG; BIOLOGICAL PRODUCT;

BEETLE; BRYOZOA; BUGULA NERITINA; CRUSTACEA; DRUG DESIGN; ECOSYSTEM; FUNGUS; HOST PATHOGEN INTERACTION; HUMAN; INTESTINE FLORA; ISOPTERA; MICROORGANISM; MOLECULAR BIOLOGY; NONHUMAN; PROGENY; REVIEW; SECONDARY METABOLISM; SYMBIONT; ANIMAL; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; MEDICINAL CHEMISTRY; MICROBIAL VIABILITY; PHYSIOLOGY; PROCEDURES; SYMBIOSIS;

ANIMALS; BIOLOGICAL PRODUCTS; CHEMISTRY, PHARMACEUTICAL; DRUG DISCOVERY; HUMANS; MICROBIAL VIABILITY; SYMBIOSIS;

EID: 84941996383     PISSN: 02536269     EISSN: 19763786     Source Type: Journal    
DOI: 10.1007/s12272-015-0639-y     Document Type: Review

References (106)

1. Anan, D.K., P. Egletton, C. Rouland-Lefèvre, T. Guldberg-Frøslev, S. Rosendahl, and J.J. Boomsma. 2002. The evolution of fungus-growing termites and their mutualistic fungal symbionts. Proceedings of the National Academy of Sciences of the United States of America 99: 14887-14892.
2. Arnison, P.G., M.J. Bibb, G. Bierbaum, A.A. Bowers, T.S. Bugni, G. Bulaj, J.A. Camarero, D.J. Campopiano, G.L. Challis, J. Clardy, P.D. Cotter, D.J. Craik, M. Dawson, E. Dittmann, S. Donadio, P.C. Dorrestein, K.D. Entian, M.A. Fischbach, J.S. Garavelli, U. Göransson, C.W. Gruber, D.H. Haft, T.K. Hemscheidt, C. Hertweck, C. Hill, A.R. Horswill, M. Jaspars, W.L. Kelly, J.P. Klinman, O.P. Kuipers, A.J. Link, W. Liu, M.A. Marahiel, D.A. Mitchell, G.N. Moll, B.S. Moore, R. Müller, S.K. Nair, I.F. Nes, G.E. Norris, B.M. Olivera, H. Onaka, M.L. Patchett, J. Piel, M.J.T. Reaney, R.P. Ross, H.G. Sahl, E.W. Schmidt, M.E. Selsted, Shen.B. Severinov, K. Sivonen, L. Smith, T.H. Stein, R.D. Süssmuth, J.R. Tagg, G.L. Tang, A.W. Truman, J.C. Vederas, C.T. Walsh, J.D. Walton, S.C. Wenzel, J.M. Willey, and W.A. van der Donk. 2013. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Natural Products Reports 30: 108-160.
3. Bi, S.F., F. Li, Y.C. Song, R.X. Tan, and H.M. Ge. 2011. New acrylamide and oxazolidin derivatives from a termite-associated Streptomyces sp. Natural Products Communications 6: 353-355.
4. Blodgett, J.A.V., D.C. Oh, S. Cao, C.R. Currie, R. Kolter, and J. Clardy. 2010. Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria. Proceedings of the National Academy of Sciences of the United States of America 107: 11692-11697.
5. Bramble, W.C., and E.C. Holst. 1940. Fungi associated with Dendroctonus frontalis in killing shortleaf pines and their effect on conduction. Phytopathology 30: 881-899.
6. Buchholz, T.J., C.M. Rath, N.B. Lopanik, N.P. Gardner, K. Hakansson, and D.H. Sherman. 2010. Polyketide β-branching in bryostatin biosynthesis: identification of surrogate acetyl-ACP donors for BryR, an HMG-ACP synthase. Chemistry and Biology 17: 1092-1100.
7. + by a variety of corals. Marine Biology 75: 151-155.
8. Carr, G., M. Poulsen, J.L. Klassen, Y. Hou, T.P. Wyche, T.S. Bugni, C.R. Currie, and J. Clardy. 2012. Microtermolides A and B from termite-associated Streptomyces sp. and structural revision of vinylamycin. Organic Letters 14: 2822-2825.
9. Chapela, I.H., S. Rehner, T.R. Schultz, and U.G. Mueller. 1994. Evolutionary history of the symbiosis between fungus-growing ants and their fungi. Science 266: 1691-1694.
10. Choi, H., N. Engene, J.E. Smith, L.B. Preskitt, and W.H. Gerwick. 2010. Crossbyanols A-D, toxic brominated polyphenyl ethers from the Hawai'ian bloom-forming cyanobacterium Leptolyngbya crossbyana. Journal of Natural Products 73: 517-522.
11. Choi, H., S.J. Mascuch, F.A. Villa, T. Byrum, M.E. Teasdale, J.E. Smith, L.B. Preskitt, D.C. Rowley, L. Gerwick, and W.H. Gerwick. 2012. Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing: synthetic derivatives and structure-activity relationships. Chemistry and Biology 19: 589-598.
12. Currie, C.R., M. Poulsen, J. Mendenhall, J.J. Boosma, and J. Billen. 2006. Coevolved crypts and exocrine glands support mutualistic bacteria in fungus-growing ants. Science 311: 81-83.
13. Currie, C.R., J.A. Scott, R.C. Summerbell, and D. Malloch. 1999. Fungus-growing ants use antibiotic-producing bacteria to control garden parasites. Nature 398: 701-704.
14. Currie, C.R., B. Wong, A.E. Stuart, T.R. Schultz, S.A. Rehner, U.G. Mueller, G.H. Sung, J. Spatafora, and N.A. Straus. 2003. Ancient tripartite coevolution in the attine ant-microbe symbiosis. Science 299: 386-388.
15. Davidson, S.K., S.W. Allen, G.E. Lim, C.M. Anderson, and M.G. Haygood. 2001. Evidence for the biosynthesis of bryostatins by the bacterial symbiont "Candidatus Endobugula sertula" of the bryozoan Bugula neritina. Applied and Environment Microbiology 67: 4531-4537.
16. Davies, J., and K.S. Ryan. 2012. Introducing the parvome: bioactive compounds in the microbial world. ACS Chemical Biology 7: 252-259.
17. DeChristopher, B., B. Loy, M. Marsden, A. Schrier, J. Zack, and P. Wender. 2012. Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro. Nature Chemistry 4: 705-710.
18. Degnan, B.M., C.J. Hawkins, M.F. Lavin, E.J. McCaffrey, D.L. Parry, A.L. van den Brenk, and D.J. Watters. 1989. New cyclic peptides with cytotoxic activity from the ascidian Lissoclinum patella. Journal of Medicinal Chemistry 32: 1349-1354.
19. Donia, M.S., B.J. Hathaway, S. Sudek, M. Haygood, M.J. Rosovitz, J. Ravel, and E.W. Schmidt. 2006. Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nature Chemical Biology 2: 729-735.
20. Etcheberrigaray, R., M. Tan, I. Dewachter, C. Kuiperi, I. Van der Auwera, S. Wera, L. Qiao, B. Bank, T.J. Nelson, A.P. Kozikowski, F. Van Leuven, and D.L. Alkon. 2004. Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 101: 11141-11146.
21. Fenical, W. 1987. Marine soft corals of the genus Pseudopterogorgia: a resource for novel anti-inflammatory diterpenoids. Journal of Natural Products 50: 1001-1008.
22. Fenical, W., and J.R. Pawlik. 1991. Defensive properties of secondary metabolites from the Caribbean gorgonian coral Erythropodium caribaeorum. Marine Ecology Progress Series 75: 1-8.
23. Fleming, A. 1929. The antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzae. British Journal of Experimental Pathology 10: 26-236.
24. Freinkman, E., D.C. Oh, J.J. Scott, C.R. Currie, and J. Clardy. 2009. Bionectriol A, a polyketide glycoside from the fungus Bionectria sp. associated with the fungus-growing ant Apterostigma dentigerum. Tetrahedron Letters 50: 6834-6837.
25. Gates, R.D., and T.D. Ainsworth. 2011. The nature and taxonomic composition of coral symbiomes as drivers of performance limits in scleractinians corals. Journal of Experimental Marine Biology and Ecology 408: 94-101.
26. Gil-Turnes, M.S., M.E. Hay, and W. Fenical. 1989. Symbiotic marine bacteria chemically defend crustacean embryos from a pathogenic fungus. Science 246: 116-118.
27. Goekjian, P.G., and M.R. Jirousek. 2001. Protein kinase C inhibitors as novel anticancer drugs. Expert Opinion on Investigational Drugs 10: 2117-2140.
28. Guo, Z.K., R.H. Jiao, H.F. Dai, W.L. Mei, R.X. Tan, and H.M. Ge. 2013. Actinotetraoses I-K: tetrasaccharide metabolites produced by an insect-derived actinobacteria, Amycolatopsis sp. HCa1. Chemistry and Biodiversity 10: 296-302.
29. Guo, Z.K., G.F. Zhang, R.H. Jiao, Y. Shen, Q. Xu, R.X. Tan, and H.M. Ge. 2012. Actinotetraoses A-H: tetrasaccharide derivatives from a grasshopper-associated Amycolatopsis sp. HCa1. Planta Medica 78: 988-994.
30. Halford, B. 2011. The bryostatins' tale. Chemical and Engineering News 89: 10-17.
31. Hayden, E.C. 2009. Fungus farmers show way to new drugs. Nature 458: 558-559.
32. Haygood, M.G., and S.K. Davidson. 1997. Small-subunit rRNA genes and in situ hybridization with oligonucleotides specific for the bacterial symbionts in the larvae of the bryozoan Bugula neritina and proposal of "Candidatus endobugula sertula". Applied and Environment Microbiology 63: 4612-4616.
33. Hildebrand, M., L.E. Waggoner, H. Liu, S. Sudek, S. Allen, C. Anderson, D.H. Sherman, and M. Haygood. 2004. bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina. Chemistry and Biology 11: 1543-1552.
34. Hirose, E., M. Hirose, and B.A. Neilan. 2006. Localization of symbiotic cyanobacteria in the colonial ascidian Trididemnum miniatum (Didemnidae, Ascidiacea). Zoological Science 23: 435-442.
35. Hofstetter, R.W., J.T. Cronin, K.D. Klepzig, J.C. Moser, and M.P. Ayres. 2006. Antagonisms, mutualisms and commensalisms affect outbreak dynamics of the southern pine beetle. Oecologia 147: 679-691.
36. Ireland, C.M., and P.J. Scheuer. 1980. Ulicyclamide and ulithiacyclamide, two new small peptides from a marine tunicate. Journal of the American Chemical Society 102: 5688-5691.
37. Kaltenpoth, M., W. Goettler, C. Dale, J.W. Stubblefield, G. Herzner, K. Roeser-Mueller, and E. Strohm. 2006. 'Candidatus streptomyces philanthi', an endosymbiotic streptomycete in the antennae of Philanthus digger wasps. International Journal of Systematic and Evolutionary Microbiology 56: 1403-1411.
38. Kaltenpoth, M., W. Gottler, G. Herzner, and E. Strohm. 2005. Symbiotic bacteria protect wasp larvae from fungal infestation. Current Biology 15: 475-479.
39. Katoh, H., T. Miura, K. Maekawa, N. Shinzato, and T. Matsumoto. 2002. Genetic variation of symbiotic fungi cultivated by the macrotermitine termite Odontotermes formosanus (Isoptera: Termitidae) in the Ryukyu Archipelago. Molecular Ecology 11: 1565-1572.
40. Keck, G.E., Y.M. Poudel, T.J. Cummins, A. Rudra, and J.A. Covel. 2011. Total synthesis of bryostatin 1. Journal of the American Chemical Society 133: 744-747.
41. Kerr, R.G., J. Lawry, and K.A. Gush. 1996. In vitro biosynthetic studies of the bryostatins, anti-cancer agents from the marine bryozoan Bugula neritina. Tetrahedron Letters 37: 8305-8308.
42. Kim, S.H., H. Ko, H.S. Bang, S.H. Park, D.G. Kim, H.C. Kwon, S.Y. Kim, J. Shin, and D.C. Oh. 2011. Coprismycins A and B, neuroprotective phenylpyridines from the dung beetle-associated bacterium Streptomyces sp. Bioorganic and Medicinal Chemistry Letters 21: 5715-5718.
43. Kim, S.H., S.H. Kwon, S.H. Park, J.K. Lee, H.S. Bang, S.J. Nam, H.C. Kwon, J. Shin, and D.C. Oh. 2013. Tripartin, a histone demethylase inhibitor from a bacterium associated with a dung beetle larva. Organic Letters 15: 1834-1837.
44. Kim, K.H., T.R. Ramadhar, C. Beemelmanns, S. Cao, M. Poulsen, C.R. Currie, and J. Clardy. 2014. Natalamycin A, an ansamycin from a termite-associated Streptomyces sp. Chemical Science 5: 4333-4338.
45. Klepzig, K.D., J.C. Moser, F.J. Lombardero, R.W. Hofstetter, and M.P. Ayres. 2001. Symbiosis and competition: complex interactions among beetles, fungi and mites. Symbiosis 30: 83-96.
46. Klepzig, K.D., and R.T. Wilkens. 1997. Competitive interactions among symbiotic fungi of the southern pine beetle. Applied and Environment Microbiology 63: 621-627.
47. Kollá, P., J. Rajchard, and Pazourek.J. Balounová. 2014. Marine natural products: bryostatins in preclinical and clinical studies. Pharmaceutical Biology 52: 237-242.
48. Kroiss, J., M. Kaltenpoth, B. Schneider, M.G. Schwinger, C. Hertweck, R.K. Maddula, E. Strohm, and S. Svatoš. 2010. Symbiotic streptomycetes provide antibiotic combination prophylaxis for wasp offspring. Nature Chemical Biology 6: 261-263.
49. Kühl, M., and A.W.D. Larkum. 2002. The microenvironment and photosynthetic performance of Prochloron sp. in symbiosis with Didemnid ascidians. In Symbiosis - mechanisms and model systems, ed. J. Seckbach, 273-290. Boston: Kluwer.
50. Lewin, R.A., and N.W. Withers. 1975. Extraordinary pigment composition of a prokaryotic alga. Nature 256: 735.
51. Littman, M.L., M.A. Pisano, and R.M. Lancaster. 1959. Induced resistance of Candida species to nystatin and amphotericin B. Antibiotics Annual 5: 981-987.
52. Liu, C.X., L. Wang, J.F. Chen, Z.Y. Guo, X. Tu, Z.S. Deng, and K. Zou. 2015. Paraconfuranones A-H, eight new furanone analogs from the insect-associated fungus Paraconithyrium brasiliense MZ-1. Magnetic Resonance in Chemistry 53: 317-322.
53. Long, P.F., W.C. Dunlap, C.N. Battershill, and M. Jaspars. 2005. Shotgun cloning and heterologous expression of the patellamide gene cluster as a strategy to achieving sustained metabolite production. ChemBioChem 6: 1760-1765.
54. Look, S.A., W. Fenical, R.S. Jacobs, and J. Clardy. 1986a. The pseudopterosins: anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae. Proceedings of the National Academy of Sciences of the United States of America 83: 6238-6240.
55. Look, S.A., W. Fenical, G. Matsumoto, and J. Clardy. 1986b. The pseudopterosins: a new class of antiinflammatory and analgesic diterpene pentosides from the marine sea whip Pseudopterogorgia elisabethae (Octocorallia). Journal of Organic Chemistry 51: 5140-5145.
56. Lopanik, N., N. Lindquist, and N. Targett. 2004. Potent cytotoxins produced by a microbial symbiont protect host larvae from predation. Oecologia 139: 131-139.
57. Lopanik, N.B., J.A. Shields, T.J. Buchholz, C.M. Rath, J. Hothersall, M.G. Haygood, K. Hakansson, C.M. Thomas, and D.H. Sherman. 2008. In vivo and in vitro trans-acylation by BryP, the putative bryostatin pathway acyltransferase derived from an uncultured marine symbiont. Chemistry and Biology 15: 1175-1186.
58. Lopanik, N.B., N.M. Targett, and N. Lindquist. 2006. Ontogeny of a symbiont-produced chemical defense in Bugula neritina (Bryozoa). Marine Ecology Progress Series 327: 183-191.
59. Lu, Y., S.K. Woo, and M.J. Krische. 2011. Total synthesis of bryostatin 7 via C-C bond-forming hydrogenation. Journal of the American Chemical Society 133: 13876-13879.
60. Mayer, A.M.S., P.B. Jacobson, W. Fenical, R.S. Jabocs, and K.B. Glaser. 1998. Pharmacological characterization of the pseudopterosins: novel anti-inflammatory natural products isolated from the Caribbean soft coral, Pseudopterogorgia elisabethae. Life Sciences 62: 401-407.
61. Mehla, R., S. Bivalkar-Mehla, R. Zhang, I. Handy, H. Albrecht, S. Giri, P. Nagarkatti, M. Nagarkatti, and A. Chauhan. 2010. Bryostatin modulates latent HIV-1 infection via PKC and AMPK signaling but inhibits acute infection in a receptor independent manner. PLoS ONE 5: e11160.
62. Morens, D.M., G.K. Folkers, and A.S. Fauci. 2004. The challenge of emerging and re-emerging infectious diseases. Nature 430: 242-249.
63. Muller, U.G., S.A. Rehner, and T.R. Schultz. 1998. The evolution of agriculture in ants. Science 281: 2034-2038.
64. Mydlarz, L.D., R.S. Jacobs, J. Boehnlein, and R.G. Kerr. 2003. Pseudopterosin biosynthesis in Symbiodinium sp., the dinoflagellate symbiont of Pseudopterogorgia elisabethae. Chemistry and Biology 10: 1051-1056.
65. Nelson, T.J., and D.L. Alkon. 2009. Neuroprotective versus tumorigenic protein kinase C activators. Trends in Biochemical Sciences 34: 136-145.
66. Newman, D.J., and G.M. Cragg. 2012. Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of Natural Products 75: 311-335.
67. Nirma, C., V. Eparvier, and D. Stien. 2013. Antifungal agents from Pseudallescheria boydii SNB-CN73 isolated from a Nasutitermes sp. termite. Journal of Natural Products 76: 988-991.
68. Oh, D.C., M. Poulsen, C.R. Currie, and J. Clardy. 2009a. Dentigerumycin: a bacterial mediator of an ant-fungus symbiosis. Nature Chemical Biology 5: 391-393.
69. Oh, D.C., M. Poulsen, C.R. Currie, and J. Clardy. 2011. Sceliphrolactam, a polyene macrocyclic lactam from a wasp-associated Streptomyces sp. Organic Letters 13: 752-755.
70. Oh, D.C., J.J. Scott, C.R. Currie, and J. Clardy. 2009b. Mycangimycin, a polyene peroxide from a mutualist Streptomyces sp. Organic Letters 11: 633-636.
71. Ortholand, J.Y., and A. Ganesan. 2004. Natural products and combinatorial chemistry: back to the future. Current Opinion in Chemical Biology 8: 271-280.
72. Park, S.H., K. Moon, H.S. Bang, S.H. Kim, D.G. Kim, K.B. Oh, J. Shin, and D.C. Oh. 2012. Tripartilactam, a cyclobutane-bearing tricyclic lactam from a Streptomyces sp. in a dung beetle's brood ball. Organic Letters 14: 1258-1261.
73. Paul, V.J. 1992. Ecology and chemical defense against predation. In Ecological roles of marine natural products, ed. V.J. Paul, 171-175. Ithaca: Cornell University Press.
74. Pavan, M., and G. Bo. 1953. Pederin, the toxic principle obtained in the crystalline state from blister beetles (Paederus fuscipes). Physiologia Comparata et Oecologia 3: 307-312.
75. Pechanova, O., W.D. Stone, W. Monroe, T.E. Nebeker, K.D. Klepzig, and C. Yuceer. 2008. Global and comparative protein profiles of the pronotum of the southern pine beetle, Dendroctonus frontalis. Insect Molecular Biology 17: 261-277.
76. Pettit, G.R., H.L. Cherry, D.L. Doubek, D.L. Herald, E. Arnold, and J. Clardy. 1982. Isolation and structure of bryostatin 1. Journal of the American Chemical Society 104: 6846-6848.
77. Piel, J. 2002. A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles. Proceedings of the National Academy of Sciences of the United States of America 99: 14002-14007.
78. Plumbi, S. 2001. Humans as the world's greatest evolutionary force. Science 29: 1786-1790.
79. Poulsen, M., C.D. Oh, J. Clardy, and C.R. Currie. 2011. Chemical analyses of wasp-associated Streptomyces bacteria reveal a prolific potential for natural products discovery. PLoS ONE 6: e16763.
80. Propper, D.J., V. Macaulay, K.J. O'Byrne, J.P. Braybrooke, S.M. Wilner, T.S. Ganesan, D.C. Talbot, and A.L. Harris. 1998. A phase II study of bryostatin 1 in metastatic malignant melanoma. British Journal of Cancer 78: 1337-1341.
81. Ritchie, K.B. 2006. Regulation of microbial populations by coral surface mucus and mucus-associated bacteria. Marine Ecology Progress Series 322: 1-14.
82. Rould-Lefevre, C. 2002. Termites: evolution, sociality, symbioses, ecology. Dordrecht: Kluwer.
83. Ruffner, D.E., E.W. Schmidt, and J.R. Heemstra. 2015. Assessing the combinatorial potential of the RiPP cyanobactin tru pathway. ACS Synthetic Biology 4: 482-492.
84. Sardar, D., E. Pierce, J.A. McIntosh, and E.W. Schmidt. 2015. Recognition sequences and substrate evolution in cyanobactin biosynthesis. ACS Synthetic Biology 4: 167-176.
85. Schaufelberger, D.E., M.P. Koleck, J.A. Beutler, A.M. Vatakis, A.B. Alvarado, P. Andrews, L.V. Marzo, G.M. Muschik, J. Roach, J.T. Ross, W.B. Lebherz, M.P. Reeves, R.M. Eberwein, L.L. Rodgers, R.P. Testerman, K.M. Snader, and S. Forenza. 1991. The large-scale isolation of bryostatin 1 from Bugula neritina following current good manufacturing practices. Journal of Natural Products 54: 1265-1270.
86. Schmidt, E.W., J.T. Nelson, D.A. Rasko, S. Sudek, J.A. Eisen, M.G. Haygood, and J. Ravel. 2005. Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proceedings of the National Academy of Sciences of the United States of America 102: 7315-7320.
87. Schmidt, E.W., S. Sudek, and M.G. Haygood. 2004. Genetic evidence supports secondary metabolic diversity in Prochloron spp., the cyanobacterial symbiont of a tropical ascidian. Journal of Natural Products 67: 1341-1345.
88. Scott, J.J., D.C. Oh, M.C. Yuceer, K.D. Klepzig, J. Clardy, and C.R. Currie. 2008. Bacterial protection of beetle-fungus mutualism. Science 322: 63.
89. Six, D.L., and K.D. Klepzig. 2004. Dendroctonus bark beetles as model systems for studies on symbiosis. Symbiosis 37: 207-232.
90. Smith, J.E., J. Kuwabara, K. Flanaga, S. duPlessis, J. Coney, J. Beets, M. Takabayashi, S. Barnes, J. Turner, D. Brown, B.K. Griesemeret, and F. Stanton. 2008. An unusual cyanobacterial bloom in Hawai'i. Coral Reefs 27: 851.
91. Strohm, E., and K.E. Linsenmair. 1995. Leaving the cradle: how beewolves (Philanthus triangulum F.) obtain the necessary spatial information for emergence. Zoology 98: 137-146.
92. Tan, Z., R.C. Turner, R.L. Leon, X. Li, J. Hongpaisan, W. Zheng, A.F. Logsdon, Z.J. Naser, D.L. Alkon, C.L. Rosen, and J.D. Huber. 2013. Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke. Stroke 44: 3490-3497.
93. Trindade-Silva, A.E., G.E. Lim-Fong, K.H. Sharp, and M.G. Haygood. 2010. Bryostatins: biological context and biotechnological prospects. Current Opinion in Biotechnology 21: 834-842.
94. Trost, B.M., and G. Dong. 2008. Total synthesis of bryostatin 16 using atom-economical and chemoselective approaches. Nature 456: 485-488.
95. Um, S., H.S. Bang, J. Shin, and D.C. Oh. 2013a. Actinofuranone C, a new 3-furanone-bearing polyketide from a dung beetle-associated bacterium. Natural Product Sciences 19: 71-75.
96. Um, S., A. Fraimout, P. Sapountzis, D.C. Oh, and M. Poulsen. 2013b. The fungus-growing termite Macrotermes natalensis harbors bacillaene-producing Bacillus sp. that inhibit potentially antagonistic fungi. Scientific Reports 3: 3250.
97. Um, S., S.H. Park, J. Kim, H.K. Park, K. Ko, H.S. Bang, S.K. Lee, J. Shin, and D.C. Oh. 2015. Coprisamides A and B, new cyclic peptides from a gut bacterium of the dung beetle Copris tripartitus. Organic Letters 17: 1272-1275.
98. Walsh, C. 2003a. Where will new antibiotics come from? Nature Reviews Microbiology 1: 65-70.
99. Walsh, C. 2003b. Antibiotics: actions, origins, resistance. Washington D. C.: ASM Press.
100. Wender, P.A., and A.J. Schrier. 2011. Total synthesis of bryostatin 9. Journal of the American Chemical Society 133: 9228-9231.
101. Withers, N., W. Vidaver, and R.A. Lewin. 1978. Pigment composition, photosynthesis and fine structure of a non-blue-green prokaryotic algal symbiont (Prochloron sp.) in a didemnid ascidian from Hawaiian waters. Phycologia 17: 167-171.
102. Woollacott, R.M. 1981. Association of bacteria with bryozoan larvae. Marine Biology 65: 155-158.
103. Woollacott, R.M., and R.L. Zimmer. 1975. A simplified placenta-like system for the transport of extraembryonic nutrients during embryogenesis of Bugula neritina (bryozoa). Journal of Morphology 147: 355-377.
104. Wright, G.D. 2007. The antibiotic resistome: the nexus of chemical and genetic diversity. Nature Reviews Microbiology 5: 175-186.
105. Wu, Q., N. Jiang, B.H. Wen, N.M. Ya, M.G. Hui, K.G. Zhi, S.W. Ng, and R.X. Tan. 2014. Antibacterial epipolythiodioxopiperazine and unprecedented sesquiterpene from Pseudallescheria boydii, a beetle (Coleptera)-associated fungus. Organic and Biomolecular Chemistry 12: 9412-9505.
106. Zhang, Y.L., H.M. Ge, W. Zhao, H. Dong, Q. Xu, S.H. Li, J. Li, J. Zhang, Y.C. Song, and R.X. Tan. 2008. Unprecedented immunosuppressive polyketides from Daldinia eschscholzii, a mantis-associated fungus. Angewandte Chemie International Edition 47: 5823-5826.