Abstract
Novel bioactive compounds are in high demand due to the development of microbial antibiotic resistance, increase in age-related diseases, and requirements for optimized manufacturing processes. The bioactive compounds can act as specific antitumor, anti-inflammatory, and antifungal compounds as well as pharmaceuticals against metabolic diseases. Bioprospecting from marine microorganisms has a tremendous potential for the discovery of novel bioactive compounds as enzymes and complex secondary metabolites for industrial as well as for biotechnological and therapeutic applications. A bioprospecting process usually begins with the isolation of a native microorganism, extraction of compounds from a culture sample, or with the isolation of environmental DNA for either heterologous expression or sequencing. Extracts from live microorganisms can be screened for bioactivity in function-based screening assays, while DNA from either the isolated microorganisms or from the environment can be screened with sequence-based screening methods or genome mining. Once a desired activity has been detected, the bioactive compound should be purified, the structure should be elucidated, and preferably its mechanism of action should be described. In this chapter, we give an overview of the bioprospecting process with special focus on compounds with therapeutic properties from marine microorganisms, and we evaluate some of the most commonly used strategies that have been used at different steps in the bioprospecting processes when searching for novel bioactive compounds.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aakvik T, Degnes KF, Dahlsrud R et al (2009) A plasmid RK2-based broad-host-range cloning vector useful for transfer of metagenomic libraries to a variety of bacterial species. FEMS Microbiol Lett 296:149–158. doi:10.1111/j.1574-6968.2009.01639.x
Adrio J, Demain A (2014) Microbial enzymes: tools for biotechnological processes. Biomolecules 4:117–139. doi:10.3390/biom4010117
Alavez S, Vantipalli MC, Zucker DJS et al (2011) Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 472:226–229. doi:10.1038/nature09873
Andries K, Dewindt B, Snoeks J et al (1992) In vitro activity of pirodavir (R 77975), a substituted phenoxy- pyridazinamine with broad-spectrum antipicornaviral activity. Antimicrob Agents Chemother 36:100–107. doi:10.1128/AAC.36.1.100
Arya U, Dwivedi H, Subramaniam JR (2009) Reserpine ameliorates Ab toxicity in the Alzheimer’s disease model in Caenorhabditis elegans. Exp Gerontol 44:462–466. doi:10.1016/j.exger.2009.02.010
Arya U, Das CK, Subramaniam JR (2010) Caenorhabditis elegans for preclinical drug discovery. Curr Sci 99:1669–1680
Ayuso-Sacido A, Genilloud O (2005) New PCR primers for the screening of NRPS and PKS-I systems in actinomycetes: detection and distribution of these biosynthetic gene sequences in major taxonomic groups. Microb Ecol 49:10–24. doi:10.1007/s00248-004-0249-6
Bachrach HL, Callis JJ, Hess WR, Patty RE (1957) A plaque assay for foot-and-mouth disease virus and kinetics of virus reproduction. Virology 4:224–236. doi:10.1016/0042-6822(57)90060-0
Barone R, De Santi C, Palma Esposito F et al (2014) Marine metagenomics, a valuable tool for enzymes and bioactive compounds discovery. Front Mar Sci 1:1–6. doi:10.3389/fmars.2014.00038
Bem AE, Velikova N, Pellicer MT et al (2015) Bacterial histidine kinases as novel antibacterial drug targets. ACS Chem Biol 10:213–224. doi:10.1021/cb5007135
Bérdy J (2005) Bioactive microbial metabolites. J Antibiot (Tokyo) 58:1–26. doi:10.1038/ja.2005.1
Bode HB, Bethe B, Hoefs R, Zeeck A (2002) Big effects from small changes: possible ways to explore nature’s chemical diversity. ChemBioChem 3:619–627
Bowman JP (2007) Bioactive compound synthetic capacity and ecological significance of marine bacterial genus Pseudoalteromonas. Mar Drugs 5:220–241
Boyd MR, Paull KD (1995) Some practical consideration and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev Res 34:91–109
Brinkhoff T, Bach G, Heidorn T et al (2004) Antibiotic production by a Roseobacter clade-affiliated species from the German Wadden Sea and its antagonistic effects on indigenous isolates. Appl Environ Microbiol 70:2560–2565. doi:10.1128/AEM.70.4.2560-2565.2003
Bruhn JB, Gram L, Belas R (2007) Production of antibacterial compounds and biofilm formation by Roseobacter species are influenced by culture conditions. Appl Environ Microbiol 73:442–450. doi:10.1128/AEM.02238-06
Burja AM, Banaigs B, Abou-Mansour E et al (2001) Marine cyanobacteria—a prolific source of natural products. Tetrahedron 57:9347–9377. doi:10.1016/S0040-4020(01)00931-0
Button DK, Schut F, Quang P et al (1993) Viability and isolation of marine bacteria by dilution culture: theory, procedures, and initial results. Appl Environ Microbiol 59:881–891
Calteau A, Fewer DP, Latifi A et al (2014) Phylum-wide comparative genomics unravel the diversity of secondary metabolism in Cyanobacteria. BMC Genom 15:977. doi:10.1186/1471-2164-15-977
Carson CF, Mee BJ, Riley TV (2002) Mechanism of action of Melaleuca alternifolia (tea tree) oil on Staphylococcus aureus determined by time-kill, lysis, leakage, and salt tolerance assays and electron microscopy. Antimicrob Agents Chemother 46:1914–1920. doi:10.1128/AAC.46.6.1914
Cha C, Gao P, Chen Y et al (1998) Production of acyl-homoserine lactone quorum-sensing signals by Gram-negative plant-associated bacteria. Mol Plant Microbe Interact 11:1119–1129
Chellaram C, Anand TP, Shanthini CF et al (2012) Bioactive peptides from epibiotic Pseudoalteromonas strain P1. APCBEE Procedia 2:37–42. doi:10.1016/j.apcbee.2012.06.008
Cimermancic P, Medema MH, Claesen J et al (2014) Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 158:412–421. doi:10.1016/j.cell.2014.06.034
Clardy J, Fischbach MA, Walsh CT (2006) New antibiotics from bacterial natural products. Nat Biotechnol 24:1541–1550. doi:10.1038/nbt1266
Cleveland J, Montville TJ, Nes IF, Chikindas ML (2001) Bacteriocins: safe, natural antimicrobials for food preservation. Int J Food Microbiol 71:1–20. doi:10.1016/S0168-1605(01)00560-8
Connon SA, Giovannoni SJ (2002) High-throughput methods for culturing microorganisms in very-low-nutrient media yield diverse new marine isolates. Appl Environ Microbiol 68:3878–3885. doi:10.1128/AEM.68.8.3878
Cooper PD (1961) The plaque assay of animal viruses. Adv Virus Res 8:319–378
Cotsonas King A, Wu L (2009) Macromolecular synthesis and membrane pertubation assay for mechanisms of action studies of antimicrobial agents. Curr Protoc Pharmacol 47:13A.7.1–13A.7.23
Cude WN, Mooney J, Tavanaei AA et al (2012) Production of the antimicrobial secondary metabolite indigoidine contributes to competitive surface colonization by the marine roseobacter Phaeobacter sp. strain Y4I. Appl Environ Microbiol 78:4771–4780. doi:10.1128/AEM.00297-12
Cuevas C, Pérez M, Martín MJ et al (2000) Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B. Org Lett 2:2545–2548. doi:10.1021/ol0062502
D’Onofrio A, Crawford JM, Stewart EJ et al (2010) Siderophores from neighboring organisms promote the growth of uncultured bacteria. Chem Biol 17:254–264. doi:10.1016/j.chembiol.2010.02.010
Davidson SK, Allen SW, Lim GE et al (2001) Evidence for the biosynthesis of bryostatins by the bacterial symbiont Candidatus Endobugula sertula of the bryozoan Bugula neritina. Appl Environ Microbiol 67:4531–4537. doi:10.1128/AEM.67.10.4531-4537.2001
de Jong A, van Hijum SAFT, Bijlsma JJE et al (2006) BAGEL: a web-based bacteriocin genome mining tool. Nucleic Acids Res 34:W273–W279. doi:10.1093/nar/gkl237
DeGroot DE, Franks DG, Higa T et al (2015) Naturally occurring marine brominated indoles are aryl hydrocarbon receptor ligands/agonists. Chem Res Toxicol 28:1176–1185. doi:10.1021/acs.chemrestox.5b00003
Denny FWJ (1995) The clinical impact of human respiratory virus infections. Am J Respir Crit Care Med 152:4–12
DeVita VT, Chu E (2008) A history of cancer chemotherapy. Cancer Res 68:8643–8653. doi:10.1158/0008-5472.CAN-07-6611
Dostal V, Roberts CM, Link CD (2010) Genetic mechanisms of coffee extract protection in a Caenorhabditis elegans model of b-amyloid peptide toxicity. Genetics 186:857–866. doi:10.1534/genetics.110.120436
Ebada SS, Edrada RA, Lin W, Proksch P (2008) Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates. Nat Protoc 3:1820–1831. doi:10.1038/nprot.2008.182
Egan S, Wiener P, Kallifidas D, Wellington EMH (2001) Phylogeny of Streptomyces species and evidence for horizontal transfer of entire and partial antibiotic gene clusters. Antonie Van Leeuwenhoek 79:127–133. doi:10.1023/A:1010296220929
Eggert US (2013) The why and how of phenotypic small-molecule screens. Nat Chem Biol 9:206–209. doi:10.1038/nchembio.1206
Ehrenreich IM, Waterbury JB, Webb EA (2005) Distribution and diversity of natural product genes in marine and freshwater cyanobacterial cultures and genomes. Appl Environ Microbiol 71:7401–7413. doi:10.1128/AEM.71.11.7401
El-Elimat T, Figueroa M, Ehrmann BM et al (2013) High-resolution MS, MS/MS, and UV database of fungal secondary metabolites as a dereplication protocol for bioactive natural products. J Nat Prod 76:1709–1716. doi:10.1021/np4004307
Eustáquio AS, Nam SJ, Penn K et al (2011) The discovery of salinosporamide K from the marine bacterium Salinispora pacifica by genome mining gives insight into pathway evolution. ChemBioChem 12:61–64. doi:10.1002/cbic.201000564
Fenical W, Jensen PR (2006) Developing a new resource for drug discovery: marine actinomycete bacteria. Nat Chem Biol 2:666–673. doi:10.1038/nchembio841
Fu CY, Tang MC, Peng C et al (2009) Biosynthesis of 3-hydroxy-5-methyl-O-methyltyrosine in the saframycin/safracin biosynthetic pathway. J Microbiol Biotechnol 19:439–446. doi:10.4014/jmb.0808.484
Fu J, Bian X, Hu S et al (2012) Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting. Nat Biotechnol 30:440–446. doi:10.1038/nbt.2183
Fuloria NK, Fuloria S (2013) Analytical & bioanalytical structural elucidation of small organic molecules by 1D, 2D and multi dimensional-solution NMR spectroscopy. J Anal Bioanal Tech S11:1–8. doi:10.4172/2155-9872.S1
Gerwick WH, Moore BS (2012) Lessons from the past and charting the future of marine natural products drug discovery and chemical biology. Chem Biol 19:85–98. doi:10.1016/j.chembiol.2011.12.014
Gerwick WH, Proteau PJ, Nagle DG et al (1994) Structure of curacin A, a novel antimitotic, antiproliferative and brine shrimp toxic natural product from the marine cyanobacterium Lyngbya majuscula. J Org Chem 59:1243–1245. doi:10.1021/jo00085a006
Giacomotto J, Ségalat L (2010) High-throughput screening and small animal models, where are we? Br J Pharmacol 160:204–216. doi:10.1111/j.1476-5381.2010.00725.x
Ginolhac A, Jarrin C, Robe P et al (2005) Type I polyketide synthases may have evolved through horizontal gene transfer. J Mol Evol 60:716–725. doi:10.1007/s00239-004-0161-1
Gonzales R, Steiner JF, Sande MA (1997) Antibiotic prescribing for adults with cold, upper respiratory tract infections, and ronchitis by ambulatory care physicians. J Am Med Assoc 278:901–904
Gonzalez ME, Alarcon B, Carrasco L (1987) Polysaccharides as antiviral agents: antiviral activity of carrageenan. Antimicrob Agents Chemother 31:1388–1393. doi:10.1128/AAC.31.9.1388
Gram L (2015) Silent clusters—speak up! Microb Biotechnol 8:13–14. doi:10.1111/1751-7915.12181
Gram L, Melchiorsen J, Bruhn JB (2010) Antibacterial activity of marine culturable bacteria collected from a global sampling of ocean surface waters and surface swabs of marine organisms. Mar Biotechnol (NY) 12:439–451. doi:10.1007/s10126-009-9233-y
Greve JM, Davis G, Meyer AM et al (1989) The major human rhinovirus receptor is ICAM-1. Cell 56:839–847. doi:10.1016/0092-8674(89)90688-0
Helfrich EJ, Reiter S, Piel J (2014) Recent advances in genome-based polyketide discovery. Curr Opin Biotechnol 29:107–115. doi:10.1016/j.copbio.2014.03.004
Hiep C, McDonough (2012) Marine biodiversity: a science roadmap for Europe. Marine Board Future Science Brief 1, European Marine Board, Ostend, Belgium. ISBN 978-2-918428-75-6
Higginbotham S, Wong WR, Linington RG et al (2014) Sloth hair as a novel source of fungi with potent anti-parasitic, anti-cancer and anti-bacterial bioactivity. PLoS ONE. doi:10.1371/journal.pone.0084549
Hoelder S, Clarke PA, Workman P (2012) Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol Oncol 6:155–176. doi:10.1016/j.molonc.2012.02.004
Hofer F, Gruenberger M, Kowalski H et al (1994) Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Nat Acad Sci USA 91:1839–1842. doi:10.1073/pnas.91.5.1839
Hoffmeister D, Keller NP (2007) Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep 24:393–416. doi:10.1039/B603084J
Holbeck SL (2004) Update on NCI in vitro drug screen utilities. Eur J Cancer 40:785–793. doi:10.1016/j.ejca.2003.11.022
Hosaka T, Ohnishi-Kameyama M, Muramatsu H et al (2009) Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12. Nat Biotechnol 27:462–464. doi:10.1038/nbt.1538
Izallalen M, Lavesque RC, Perret X et al (2002) Broad-host-range mobilizable suicide vectors for promoter trapping in gram-negative bacteria. Biotechniques 33:1038–1043. doi:10.2144/000113156
Jensen PR, Chavarria KL, Fenical W et al (2014) Challenges and triumphs to genomics-based natural product discovery. J Ind Microbiol Biotechnol 41:203–209. doi:10.1007/s10295-013-1353-8
Jin M, Fischbach MA, Clardy J (2006) A biosynthetic gene cluster for the acetyl-CoA carboxylase inhibitor andrimid. J Am Chem Soc 128:10660–10661. doi:10.1021/ja063194c
Johnston MD, Hanlon GW, Denyer SP, Lambert RJW (2003) Membrane damage to bacteria caused by single and combined biocides. J Appl Microbiol 94:1015–1023. doi:10.1046/j.1365-2672.2003.01923.x
Kapuscinski J (1979) DAPI: a DNA-specific fluorescent probe. Biotech Histochem 70:220–233. doi:10.3109/10520299509108199
Kell DB (2013) Finding novel pharmaceuticals in the systems biology era using multiple effective drug targets, phenotypic screening and knowledge of transporters: where drug discovery went wrong and how to fix it. FEBS J 280:5957–5980. doi:10.1111/febs.12268
Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism—from biochemistry to genomics. Nat Rev Microbiol 3:937–947. doi:10.1038/nrmicro1286
Khan ST, Komaki H, Motohashi K et al (2011) Streptomyces associated with a marine sponge Haliclona sp.; biosynthetic genes for secondary metabolites and products. Environ Microbiol 13:391–403. doi:10.1111/j.1462-2920.2010.02337.x
Kildgaard S, Mansson M, Dosen I et al (2014) Accurate dereplication of bioactive secondary metabolites from marine-derived fungi by UHPLC-DAD-QTOFMS and a MS/HRMS library. Mar Drugs 12:3681–3705. doi:10.3390/md12063681
Klitgaard A, Iversen A, Andersen MR et al (2014) Aggressive dereplication using UHPLC–DAD–QTOF: screening extracts for up to 3000 fungal secondary metabolites. Anal Bioanal Chem 406:1933–1943. doi:10.1007/s00216-013-7582-x
Kogure K, Simidu U, Taga N (1979) A tentative direct microscopic method for counting living marine bacteria. Can J Microbiol 25:415–420. doi:10.1139/m79-063
Kondo T, Strayer CA, Kulkarni RD et al (1993) Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria. Proc Nat Acad Sci USA 90:5672–5676. doi:10.1073/pnas.90.12.5672
Kotz J (2012) Phenotypic screening, take two. Sci Exch 5:1–3. doi:10.1038/scibx.2012.380
Kwan EE, Huang SG (2008). Structural elucidation with NMR spectroscopy: practical strategies for organic chemists. Eur J Org Chem 2671–2688. doi:10.1002/ejoc.200700966
Lale R, Brautaset T, Valla S (2011) Broad-host-range plasmid vectors for gene expression in bacteria. In: Williams JA (ed) Strain engineering:methods and protocols. Humana Press, Totowa, pp 327–343
Lane AL, Moore BS (2012) A sea of biosynthesis: marine natural products meet the molecular age. Nat Prod Rep 28:411–428. doi:10.1039/c0np90032j.A
Lechner A, Eustáquio AS, Gulder TAM et al (2011) Selective overproduction of the proteasome inhibitor salinosporamide A via precursor pathway regulation. Chem Biol 18:1527–1536. doi:10.1016/j.chembiol.2011.10.014
Ling LL, Schneider T, Peoples AJ et al (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517:455–459. doi:10.1038/nature14098
Loeschcke A, Markert A, Wilhelm S et al (2013) TREX: a universal tool for the transfer and expression of biosynthetic pathways in bacteria. ACS Synth Biol 2:22–33. doi:10.1021/sb3000657
Lombó F, Velasco A, Castro A et al (2006) Deciphering the biosynthesis pathway of the antitumor thiocoraline from a marine actinomycete and its expression in two Streptomyces species. ChemBioChem 7:366–376. doi:10.1002/cbic.200500325
Lozupone CA, Knight R (2007) Global patterns in bacterial diversity. Proc Nat Acad Sci 104:11436–11440. doi:10.1073/pnas.0611525104
Luesch H, Moore RE, Paul VJ et al (2001) Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. J Nat Prod 64:907–910. doi:10.1021/np010049y
Lynch MD, Gill RT (2006) Broad host range vectors for stable genomic library construction. Biotechnol Bioeng 94:151–158. doi:10.1002/bit
Machado H, Sonnenschein EC, Melchiorsen J, Gram L (2015) Genome mining reveals unlocked bioactive potential of marine gram-negative bacteria. BMC Genom 16:158. doi:10.1186/s12864-015-1365-z
Macintyre L, Zhang T, Viegelmann C et al (2014) Metabolomic tools for secondary metabolite discovery from marine microbial symbionts. Mar Drugs 12:3416–3448. doi:10.3390/md12063416
Manivasagan P, Venkatesan J, Sivakumar K, Kim SK (2014) Pharmaceutically active secondary metabolites of marine actinobacteria. Microbiol Res 169:262–278. doi:10.1016/j.micres.2013.07.014
Mansson M, Vynne NG, Klitgaard A et al (in prep) Integrated metabolomic and genomic mining of the biosynthetic potential of bacteria
Mansson M, Phipps RK, Gram L et al (2010) Explorative solid-phase extraction (E-SPE) for accelerated microbial natural product discovery, dereplication, and purification. J Nat Prod 73:1126–1132. doi:10.1021/np100151y
Mansson M, Gram L, Larsen TO (2011) Production of bioactive secondary metabolites by marine Vibrionaceae. Mar Drugs 9:1440–1468. doi:10.3390/md9091440
Marmann A, Aly AH, Lin W et al (2014) Co-cultivation - A powerful emerging tool for enhancing the chemical diversity of microorganisms. Mar Drugs 12:1043–1065. doi:10.3390/md12021043
Marsh SE, Blurton-Jones M (2012) Examining the mechanisms that link β-amyloid and α-synuclein pathologies. Alzheimers Res Ther. doi:10.1186/alzrt109
Medema MH, Blin K, Cimermancic P et al (2011) antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39:W339–W346. doi:10.1093/nar/gkr466
Moffat JG, Rudolph J, Bailey D (2014) Phenotypic screening in cancer drug discovery—past, present and future. Nat Rev Drug Discov 13:588–602. doi:10.1038/nrd4366
Molinski TF, Dalisay DS, Lievens SL, Saludes JP (2009) Drug development from marine natural products. Nat Rev Drug Discov 8:69–85. doi:10.1038/nrd2487
Nayar AS, Dougherty TJ, Ferguson KE et al (2015) Novel antibacterial targets and compounds revealed by a high throughput cell wall reporter assay. J Bacteriol 197:1726–1734. doi:10.1128/JB.02552-14
Nichols D, Cahoon N, Trakhtenberg EM et al (2010) Use of Ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl Environ Microbiol 76:2445–2450. doi:10.1128/AEM.01754-09
Nicolaus B, Kambourova M, Oner ET (2010) Exopolysaccharides from extremophiles: from fundamentals to biotechnology. Environ Technol 31:1145–1158. doi:10.1080/09593330903552094
Nielsen A, Mansson M, Wietz M et al (2012) Nigribactin, a novel siderophore from Vibrio nigripulchritudo, modulates Staphylococcus aureus virulence gene expression. Mar Drugs 10:2584–2595. doi:10.3390/md10112584
Nielsen A, Mansson M, Bojer MS et al (2014) Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils. PLoS ONE 9:e84992. doi:10.1371/journal.pone.0084992
Nonejuie P, Burkart M, Pogliano K, Pogliano J (2013) Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules. Proc Nat Acad Sci 110:16169–16174. doi:10.1073/pnas.1311066110
O’Connor M, Peifer M, Bender W (1989) Construction of large DNA segments in Escherichia coli. Science 244:1307–1312. doi:10.1111/j.1464-410X.1987.tb09132.x
O’Neill AJ, Miller K, Oliva B, Chopra I (2004) Comparison of assays for detection of agents causing membrane damage in Staphylococcus aureus. J Antimicrob Chemother 54:1127–1129. doi:10.1093/jac/dkh476
Ongley SE, Bian X, Neilan BA, Müller R (2013) Recent advances in the heterologous expression of microbial natural product biosynthetic pathways. Nat Prod Rep 30:1121. doi:10.1039/c3np70034h
Pérez M, Schleissner C, Rodríguez P et al (2009) PM070747, a new cytotoxic angucyclinone from the marine-derived Saccharopolyspora taberi PEM-06-F23-019B. J Antibiot (Tokyo) 62:167–169. doi:10.1038/ja.2008.27
Pettit GR, Kamano Y, Herald CL et al (1993) Isolation of dolastatins 10–15 from the marine mollusc Dolabella auricularia. Tetrahedron 49:9151–9170. doi:10.1016/0040-4020(93)80003-C
Piel J, Hui D, Wen G et al (2004) Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei. Proc Nat Acad Sci 101:16222–16227. doi:10.1073/pnas.0405976101
Pogliano J, Osborne N, Sharp MD et al (1999) A vital stain for studying membrane dynamics in bacteria: a novel mechanism controlling septation during Bacillus subtilis sporulation. Mol Microbiol 31:1149–1159. doi:10.1046/j.1365-2958.1999.01255.x
Proksch P, Edrada RA, Ebel R (2002) Drugs from the seas—current status and microbiological implications. Appl Microbiol Biotechnol 59:125–134. doi:10.1007/s00253-002-1006-8
Ramm W, Schatton W, Wagner-Döbler I et al (2004) Diglucosyl-glycerolipids from the marine sponge-associated Bacillus pumilus strain AAS3: their production, enzymatic modification and properties. Appl Microbiol Biotechnol 64:497–504. doi:10.1007/s00253-003-1471-8
Rasmussen TB, Givskov M (2006) Quorum sensing inhibitors: a bargain of effects. Microbiology 152:895–904. doi:10.1099/mic.0.28601-0
Rath C, Janto B, Earl J et al (2011) Meta-omic characterization of the marine invertebrate microbial consortium that produces the chemotherapeutic natural product ET-743. ACS Chem Biol 6:1244–1256
Rediers H, Rainey PB, Vanderleyden J, De Mot R (2005) Unraveling the secret lives of bacteria: use of in vivo expression technology and differential fluorescence induction promoter traps as tools for exploring niche-specific gene expression. Microbiol Mol Biol Rev 69:217–261. doi:10.1128/MMBR.69.2.217
Reen F, Gutiérrez-Barranquero J, Dobson A et al (2015) Emerging concepts promising new horizons for marine biodiscovery and synthetic biology. Mar Drugs 13:2924–2954
Romero F, Espliego F, Pérez Baz J et al (1997) Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activities. J Antibiot (Tokyo) 50:734–737
Ross AC, Gulland LES, Dorrestein PC, Moore BS (2015) Targeted capture and heterologous expression of the Pseudoalteromonas alterochromide gene cluster in Escherichia coli represents a promising natural product exploratory platform. ACS Synth Biol 4:414–420. doi:10.1021/sb500280q
Sams-Dodd F (2005) Target-based drug discovery: is something wrong? Drug Discov Today 10:139–147. doi:10.1016/S1359-6446(04)03316-1
Sarkar S, Saha M, Roy D et al (2008) Enhanced production of antimicrobial compounds by three salt-tolerant actinobacterial strains isolated from the Sundarbans in a niche-mimic bioreactor. Mar Biotechnol 10:518–526. doi:10.1007/s10126-008-9090-0
Schäberle TF, Goralski E, Neu E et al (2010) Marine myxobacteria as a source of antibiotics—comparison of physiology, polyketide-type genes and antibiotic production of three new isolates of Enhygromyxa salina. Mar Drugs 8:2466–2479. doi:10.3390/md8092466
Schatz A, Bugie E, Waksman SA (1944) Streptomycin, a substance ehibiting antibiotic activity against gram-negative bacteria. Exp Biol Med 55:66–69
Schiewe HJ, Zeeck A (1999) Cineromycins, gamma-butyrolactones and ansamycins by analysis of the secondary metabolite pattern created by a single strain of Streptomyces. J Antibiot (Tokyo) 52:635–642
Schleissner C, Pérez M, Losada A et al (2011) Antitumor actinopyranones produced by Streptomyces albus POR-04-15-053 isolated from a marine sediment. J Nat Prod 74:1590–1596. doi:10.1021/np200196j
Schmid A, Dordick JS, Hauer B et al (2001) Industrial biocatalysis today and tomorrow. Nature 409:258–268. doi:10.1038/35051736
Schmidtke M, Schnittler U, Jahn B et al (2001) A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1. J Virol Methods 95:133–143
Schmitz JE, Daniel A, Collin M et al (2008) Rapid DNA library construction for functional genomic and metagenomic screening. Appl Environ Microbiol 74:1649–1652. doi:10.1128/AEM.01864-07
Seyedsayamdost MR (2014) High-throughput platform for the discovery of elicitors of silent bacterial gene clusters. Proc Nat Acad Sci USA 111:7266–7271. doi:10.1073/pnas.1400019111
Sharma SV, Haber DA, Settleman J (2010) Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents. Nat Rev Cancer 10:241–253. doi:10.1038/nrc2820
Shizuya H, Kouros-Mehr H (2001) The development and applications of the bacterial artificial chromosome cloning system. Keio J Med 50:26–30. doi:10.2302/kjm.50.26
Simon C, Daniel R (2011) Metagenomic analyses: past and future trends. Appl Environ Microbiol 77:1153–1161. doi:10.1128/AEM.02345-10
Stevens DC, Conway KR, Pearce N et al (2013) Alternative sigma factor over-expression enables heterologous expression of a type II polyketide biosynthetic pathway in Escherichia coli. PLoS ONE 8:e64858. doi:10.1371/journal.pone.0064858
Stevenson CS, Capper EA, Roshak AK et al (2002) Scytonemin—a marine natural product inhibitor of kinases key in hyperproliferative inflammatory diseases. Inflamm Res 51:112–114. doi:10.1007/BF02684014
Stewart EJ (2012) Growing unculturable bacteria. J Bacteriol 194:4151–4160. doi:10.1128/JB.00345-12
Sun D, Cohen S, Mani N et al (2002) A pathway-specific cell based screening system to detect bacterial cell wall inhibitors. J Antibiot (Tokyo) 55:279–287
Sutherland IW (2001) Microbial polysaccharides from Gram-negative bacteria. Int Dairy J 11:663–674. doi:10.1016/S0958-6946(01)00112-1
Swinney DC (2013) Phenotypic vs. target-based drug discovery for first-in-class medicines. Clin Pharmacol Ther 93:299–301. doi:10.1038/clpt.2012.236
Swinney DC, Anthony J (2011) How were new medicines discovered? Nat Rev Drug Discov 10:507–519. doi:10.1038/nrd3480
Tan LT (2007) Bioactive natural products from marine cyanobacteria for drug discovery. Phytochemistry 68:954–979. doi:10.1016/j.phytochem.2007.01.012
Tawfike AF, Viegelmann C, Edrada-Ebel R (2013) Metabolomics and dereplication strategies in natural products. In: Roessner U, Dias DA (eds) Metabolomics tools for natural product discovery. Humana Press, Totowa, pp 227–244
Thaker MN, Wang W, Spanogiannopoulos P et al (2013) Identifying producers of antibacterial compounds by screening for antibiotic resistance. Nat Biotechnol 31:922–927. doi:10.1038/nbt.2685
Traxler MF, Watrous JD, Alexandrov T et al (2013) Interspecies interactions stimulate diversification of the Streptomyces coelicolor secreted metabolome. MBio 4:e00459–13–e00459–13. doi:10.1128/mBio.00459-13
Tsukimoto M, Nagaoka M, Shishido Y et al (2011) Bacterial production of the tunicate-derived antitumor cyclic depsipeptide didemnin B. J Nat Prod 74:2329–2331. doi:10.1021/np200543z
Urban A, Eckermann S, Fast B et al (2007) Novel whole-cell antibiotic biosensors for compound discovery. Appl Environ Microbiol 73:6436–6443. doi:10.1128/AEM.00586-07
van Pée KH (1996) Biosynthesis of halogenated methanes. Ann Rev Microbiol 375–399
Velasco A, Acebo P, Gomez A et al (2005) Molecular characterization of the safracin biosynthetic pathway from Pseudomonas fluorescens A2-2: designing new cytotoxic compounds. Mol Microbiol 56:144–154. doi:10.1111/j.1365-2958.2004.04433.x
Vichai V, Kirtikara K (2006) Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 1:1112–1116. doi:10.1038/nprot.2006.179
Villa FA, Lieske K, Gerwick L (2010) Selective MyD88-dependent pathway inhibition by the cyanobacterial natural product malyngamide F acetate. Eur J Pharmacol 629:140–146. doi:10.1021/ac901991x
Vynne NG, Mansson M, Nielsen KF, Gram L (2011) Bioactivity, chemical profiling, and 16S rRNA-based phylogeny of Pseudoalteromonas strains collected on a global research cruise. Mar Biotechnol 13:1062–1073. doi:10.1007/s10126-011-9369-4
Vynne NG, Mansson M, Gram L (2012) Gene sequence based clustering assists in dereplication of Pseudoalteromonas luteoviolacea strains with identical inhibitory activity and antibiotic production. Mar Drugs 10:1729–1740. doi:10.3390/md10081729
Wagenaar MM (2008) Pre-fractionated microbial samples—the second generation natural products library at Wyeth. Molecules 13:1406–1426. doi:10.3390/molecules13061406
Wang G, Hosaka T, Ochi K (2008) Dramatic activation of antibiotic production in Streptomyces coelicolor by cumulative drug resistance mutations. Appl Environ Microbiol 74:2834–2840. doi:10.1128/AEM.02800-07
Watve M, Tickoo R, Jog M, Bhole B (2001) How many antibiotics are produced by the genus Streptomyces? Arch Microbiol 176:386–390. doi:10.1007/s002030100345
Weber T (2014) In silico tools for the analysis of antibiotic biosynthetic pathways. Int J Med Microbiol 304:230–235. doi:10.1016/j.ijmm.2014.02.001
Wenzel SC, Gross F, Zhang Y et al (2005) Heterologous expression of a myxobacterial natural products assembly line in pseudomonads via Red/ET recombineering. Chem Biol 12:349–356. doi:10.1016/j.chembiol.2004.12.012
Whalen KE, Poulson-Ellestad KL, Deering RW et al (2015) Enhancement of antibiotic activity against multidrug-resistant bacteria by the efflux pump inhibitor 3,4-dibromopyrrole-2,5-dione isolated from a Pseudoalteromonas sp. J Nat Prod 78:402–412. doi:10.1021/np500775e
Wietz M, Mansson M, Gotfredsen CH et al (2010) Antibacterial compounds from marine Vibrionaceae isolated on a global expedition. Mar Drugs 8:2946–2960. doi:10.3390/md8122946
Wietz M, Mansson M, Gram L (2011) Chitin stimulates production of the antibiotic andrimid in a Vibrio coralliilyticus strain. Environ Microbiol Rep 3:559–564. doi:10.1111/j.1758-2229.2011.00259.x
Williamson LL, Borlee BR, Schloss PD et al (2005) Intracellular screen to identify metagenomic clones that induce or inhibit a quorum-sensing biosensor. Appl Environ Microbiol 71:6335–6344. doi:10.1128/AEM.71.10.6335-6344.2005
Wilson MC, Piel J (2013) Metagenomic approaches for exploiting uncultivated bacteria as a resource for novel biosynthetic enzymology. Chem Biol 20:636–647. doi:10.1016/j.chembiol.2013.04.011
Wilson MC, Mori T, Rückert C et al (2014) An environmental bacterial taxon with a large and distinct metabolic repertoire. Nature 506:58–62. doi:10.1038/nature12959
Wong WR, Oliver AG, Linington RG (2012) Development of antibiotic activity profile screening for the classification and discovery of natural product antibiotics. Chem Biol 19:1483–1495. doi:10.1016/j.chembiol.2012.09.014
Woodhouse JN, Fan L, Brown MV et al (2013) Deep sequencing of non-ribosomal peptide synthetases and polyketide synthases from the microbiomes of Australian marine sponges. ISME J 7:1842–1851. doi:10.1038/ismej.2013.65
World Health Organization (2014) Antimicrobial resistance: global report on surveillance
Xu Y, Kersten RD, Nam SJ et al (2012) Bacterial biosynthesis and maturation of the didemnin anti-cancer agents. J Am Chem Soc 134:8625–8632. doi:10.1021/ja301735a
Yamanaka K, Reynolds KA, Kersten RD et al (2014) Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A. Proc Nat Acad Sci 111:1957–1962. doi:10.1073/pnas.1319584111
Yan L, Boyd KG, Grant Burgess J (2002) Surface attachment induced production of antimicrobial compounds by marine epiphytic bacteria using modified roller bottle cultivation. Mar Biotechnol 4:356–366. doi:10.1007/s10126-002-0041-x
Yan L, Boyd KG, Adams DR, Burgess JG (2003) Biofilm-specific cross-species induction of antimicrobial compounds in bacilli. Appl Environ Microbiol 69:3719–3727. doi:10.1128/AEM.69.7.3719
Yang JY, Sanchez LM, Rath CM et al (2013) Molecular networking as a dereplication strategy. J Nat Prod 76:1686–1699. doi:10.1021/np400413s
Yin J, Straight PD, Hrvatin S et al (2007) Genome-wide high-throughput mining of natural-product biosynthetic gene clusters by phage display. Chem Biol 14:303–312. doi:10.1016/j.chembiol.2007.01.006
Zhang J, Yang PL, Gray NS (2009) Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 9:28–39. doi:10.1038/nrc2559
Zhang Y, Huang H, Xu S et al (2015) Activation and enhancement of Fredericamycin A production in deepsea-derived Streptomyces somaliensis SCSIO ZH66 by using ribosome engineering and response surface methodology. Microb Cell Fact 14:64. doi:10.1186/s12934-015-0244-2
Zheng W, Thorne N, McKew JC (2013) Phenotypic screens as a renewed approach for drug discovery. Drug Discov Today 18:1067–1073. doi:10.1016/j.drudis.2013.07.001
Ziemert N, Podell S, Penn K et al (2012) The natural product domain seeker NaPDoS: a phylogeny based bioinformatic tool to classify secondary metabolite gene diversity. PLoS ONE 7:e34064. doi:10.1371/journal.pone.0034064
Ziemert N, Lechner A, Wietz M et al (2014) Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora. Proc Nat Acad Sci 111:E1130–E1139. doi:10.1073/pnas.1324161111
Acknowledgments
The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no 311975. This publication reflects the views only of the author, and the European Union cannot be held responsible for any use which may be made of the information contained therein (CS, FC, and MST). SG was funded by an Early Stage Researchers Grant, “BacTory”, from the People Programme (Marie Curie Actions) No. 317058 of the European Union’s Seventh Framework Programme FP7-People-2012-ITN.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Giubergia, S. et al. (2016). Screening Microorganisms for Bioactive Compounds. In: Stal, L., Cretoiu, M. (eds) The Marine Microbiome. Springer, Cham. https://doi.org/10.1007/978-3-319-33000-6_13
Download citation
DOI: https://doi.org/10.1007/978-3-319-33000-6_13
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-32998-7
Online ISBN: 978-3-319-33000-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)