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Grand Challenges in Marine Biotechnology: Overview of Recent EU-Funded Projects

  • Chiara Lauritano
  • Adrianna Ianora
Chapter
Part of the Grand Challenges in Biology and Biotechnology book series (GCBB)

Abstract

Several EU projects funded during the FP7 programme and currently under the topic ‘Blue Growth’ of Horizon 2020 aim at improving the exploitation of marine organisms for several biotechnological applications (e.g. pharmaceutical, nutraceutical, cosmeceutical, bioenergy and other industrial applications). Here we focus only on those related to marine drug discovery such as BAMMBO, BlueGenics, GIAVAP, LIPOYEASTS, MaCuMBA, MAMBA, MAREX, MarineBiotech, PharmaSea, PolyModE, SeaBioTech, SUNBIOPATH, EMBRIC, INMARE, NoMorFilm and TASCMAR. We describe the major achievements in this field in terms of improved sampling in extreme environments, optimization in cultivation methods with the creation of ad hoc systems and bioreactors/raceway ponds, speeding up the production of a specific product by genetically modifying microorganisms and sequencing genomes/transcriptomes of marine species in order to identify enzymes of industrial interest or gene clusters responsible for the synthesis of bioactives. Several enzymes and new metabolites have been found allowing for important discoveries and new products for development in different market sectors: health, personal care, cosmetics and nutrition. We also discuss the urgent need to find new funding opportunities in H2020 that will allow candidate lead compounds identified by these projects to advance to preclinical testing in order to assess chemical, biological and toxicological properties. Overcoming these difficulties would allow marine drug discovery to reach its full potential, thereby supporting the development of blue biotechnology in Europe.

Notes

Acknowledgements

We thank Flora Palumbo from Stazione Zoologica Anton Dohrn for the graphics.

References

  1. 1.
    Blunt JW, Copp BR, Keyzers RA et al (2015) Marine natural products. Nat Prod Rep 32:116–211CrossRefGoogle Scholar
  2. 2.
    Jaspars M, De Pascale D, Andersen JH et al (2016) The marine biodiscovery pipeline and ocean medicines of tomorrow. J Mar Biol Assoc UK 96(1):151–158.  https://doi.org/10.1017/S0025315415002106 CrossRefGoogle Scholar
  3. 3.
    Romano G, Costantini M, Sansone C et al (2017) Marine microorganisms as a promising and sustainable source of bioactive molecules. Mar Environ Res 128:58–69.  https://doi.org/10.1016/j.marenvres.2016.05.002 CrossRefPubMedGoogle Scholar
  4. 4.
    Reen F, Gutierrez-Barranquero J, Dobson A et al (2015) Emerging concepts promising new horizons for marine biodiscovery and synthetic biology. Mar Drugs 13(5):2924–2954.  https://doi.org/10.3390/md13052924 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Hurst D, Børresen T, Almesjö L et al (2016) Marine biotechnology strategic research and innovation roadmap: insights to the future direction of European marine biotechnology. Marine Biotechnology ERA-NET, OstendGoogle Scholar
  6. 6.
    Jeffryes C, Rosenberger J, Rorrer GL (2013) Fed-batch cultivation and bioprocess modeling of Cyclotella sp. for enhanced fatty acid production by controlled silicon limitation. Algal Res 2(1):16–27.  https://doi.org/10.1016/j.algal.2012.11.002 CrossRefGoogle Scholar
  7. 7.
    Alves C, Pinteus S, Horta A et al (2016) High cytotoxicity and anti-proliferative activity of algae extracts on an in vitro model of human hepatocellular carcinoma. SpringerPlus 5:1339.  https://doi.org/10.1186/s40064-016-2938-2 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Horta A, Pinteus S, Alves C et al (2014) Antioxidant and antimicrobial potential of the bifurcaria bifurcata epiphytic bacteria. Mar Drugs 12(3):1676–1689.  https://doi.org/10.3390/md12031676 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rodrigues D, Alves C, Horta A et al (2015) Antitumor and antimicrobial potential of bromoditerpenes isolated from the red alga, Sphaerococcus coronopifolius. Mar Drugs 13(2):713–726.  https://doi.org/10.3390/md13020713 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bondu S, Genta-Jouve G, Leiros M et al (2012) Additional bioactive guanidine alkaloids from the Mediterranean sponge Crambe crambe. RSC Adv 2(7):2828–2835.  https://doi.org/10.1039/c2ra00045h CrossRefGoogle Scholar
  11. 11.
    Alfonso A, Pazos MJ, Fernández-Araujo A et al (2014) Surface plasmon resonance biosensor method for palytoxin detection based on Na+,K+-ATPase affinity. Toxins 6(1):96–107.  https://doi.org/10.3390/toxins6010096 CrossRefGoogle Scholar
  12. 12.
    Fraga M, Vilariño N, Louzao MC et al (2013) Multidetection of paralytic, diarrheic, and amnesic shellfish toxins by an inhibition immunoassay using a microsphere-flow cytometry system. Anal Chem 85(16):7794–7802.  https://doi.org/10.1021/ac401146m CrossRefPubMedGoogle Scholar
  13. 13.
    Sanchez JA, Otero P, Alfonso A et al (2014) Detection of anatoxin-a and three analogs in Anabaena spp. cultures: new fluorescence polarization assay and toxin profile by LC-MS/MS. Toxins 6(2):402–415.  https://doi.org/10.3390/toxins6020402 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Vilarino N, Louzao MC, Fraga M et al (2013) Innovative detection methods for aquatic algal toxins and their presence in the food chain. Anal Bioanal Chem 405(24):7719–7732.  https://doi.org/10.1007/s00216-013-7108-6 CrossRefPubMedGoogle Scholar
  15. 15.
    Megumi Mizuno C, Ghai R, Rodriguez-Valera F (2014) Evidence for metaviromic islands in marine phages. Front Microbiol 5:27.  https://doi.org/10.3389/fmicb.2014.00027 CrossRefGoogle Scholar
  16. 16.
    Rodriguez-Valera F, Megumi Mizuno C, Ghaia R (2014) Tales from a thousand and one phages. Bacteriophage 4(2):e28265.  https://doi.org/10.4161/bact.28265 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Balzano S, Gourvil P, Siano R et al (2012) Diversity of cultured photosynthetic flagellates in the northeast Pacific and Arctic Oceans in summer. Biogeosciences 9(11):4553–4571.  https://doi.org/10.5194/bg-9-4553-2012 CrossRefGoogle Scholar
  18. 18.
    Boeuf D, Cottrell MT, Kirchman DL et al (2013) Summer community structure of aerobic anoxygenic phototrophic bacteria in the Western Arctic Ocean. FEMS Micriobiol Ecol 85(3):417–432. http://femsec.oxfordjournals.org/content/85/3/417 CrossRefGoogle Scholar
  19. 19.
    Dia A, Guillou L, Mauger S et al (2014) Spatiotemporal changes in the genetic diversity of harmful algal blooms caused by the toxic dinoflagellate. Mol Ecol 23:549–560.  https://doi.org/10.1111/mec.12617 CrossRefPubMedGoogle Scholar
  20. 20.
    Ghai R, Megumi Mizuno C, Picazo A et al (2013) Metagenomics uncovers a new group of low GC and ultra-small marine Actinobacteria. Sci Rep 3:2471. http://www.nature.com/srep/2013/130820/srep02471/full/srep02471.html CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Gonzaga A, López-Pérez M, Martin-Cuadrado AB et al (2012a) Genome sequence of the copiotrophic marine bacterium Alteromonas macleodii strain ATCC 27126T. J Bacteriol 194(24):6998. http://jb.asm.org/content/194/24/6998 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Gonzaga A, Martin-Cuadrado AB, López-Pérez M et al (2012b) Polyclonality of concurrent natural populations of Alteromonas macleodii. Genome Biol Evol 4(12):1360–1374. http://gbe.oxfordjournals.org/content/4/12/1360 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Humily F, Farrant GK, Marie D et al (2014) Development of a targeted metagenomic approach to study a genomic region involved in light harvesting in marine. FEMS Microbiol Ecol 88(2):231–249.  https://doi.org/10.1111/1574-6941.12285 CrossRefPubMedGoogle Scholar
  24. 24.
    López-Pérez M, Gonzaga A, Ivanova EP et al (2014) Genomes of Alteromonas australica, a world apart. BMC Genomics 15:483.  https://doi.org/10.1186/1471-2164-15-483 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Paul R, Jinkerson RE, Buss K et al (2014) Draft genome sequence of the filamentous cyanobacterium Leptolyngbya sp. strain heron island j, exhibiting chromatic acclimation. Genome Announc 2(1):e01166-13.  https://doi.org/10.1128/genomeA.01166-13 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Probert I, Siano R, Poirier C et al (2014) Not. Brandtodinium gen. nov. and B. nutricula comb. Nov. (Dinophyceae), a dinoflagellate commonly found in symbiosis with polycystine radiolarians. J Phycol 50(2):388–399.  https://doi.org/10.1111/jpy.12174 CrossRefPubMedGoogle Scholar
  27. 27.
    Steglich C, Stazic D, Lott SC et al (2014) Dataset for metatranscriptome analysis of Prochlorococcus-rich marine picoplankton communities in the Gulf of Aqaba, Red Sea. Mar Genomics 19:5–7.  https://doi.org/10.1016/j.margen.2014.10.009 CrossRefPubMedGoogle Scholar
  28. 28.
    Pfreundt U, Kopf M, Belkin N et al (2014) The primary transcriptome of the marine diazotroph Trichodesmium erythraeum IMS101. Sci Report 4:6187.  https://doi.org/10.1038/srep06187 CrossRefGoogle Scholar
  29. 29.
    Pfreundt U, Miller D, Adusumilli L et al (2014) Depth dependent metatranscriptomes of the marine pico-/nanoplanktonic communities in the Gulf of Aqaba/Eilat during seasonal deep mixing. Mar Genomics 18:93–95.  https://doi.org/10.1016/j.margen.2014.06.005 CrossRefPubMedGoogle Scholar
  30. 30.
    Voigt K, Sharma CM, Mitschke J et al (2014) Comparative transcriptomics of two environmentally relevant cyanobacteria reveals unexpected transcriptome diversity. ISME J 8:2056–2068.  https://doi.org/10.1038/ismej.2014.57 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Voß B, Bolhuis H, Fewer DP et al (2013) Insights into the physiology and ecology of the brackish-water-adapted cyanobacterium Nodularia spumigena CCY9414 based on a genome-transcriptome analysis. PLoS One 8(3):e60224.  https://doi.org/10.1371/journal.pone.0060224 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lepelletier F, Karpov SA, Le Pansee S et al (2014a) Parvilucifera rostrata sp. nov. (Perkinsozoa), a novel parasitoid that infects planktonic dinoflagellates. Protist 165(1):31–49.  https://doi.org/10.1016/j.protis.2013.09.005 CrossRefPubMedGoogle Scholar
  33. 33.
    Lepelletier F, Karpov SA, Alacid E et al (2014b) Dinomyces arenysensis gen. et sp. nov. (Rhizophydiales, Dinomycetaceae fam. nov.), a chytrid infecting marine dinoflagellates. Protist 165(2):230–244.  https://doi.org/10.1016/j.protis.2014.02.004 CrossRefPubMedGoogle Scholar
  34. 34.
    Marie D, Rigaut-Jalabert F, Vaulot D (2014) An improved protocol for flow cytometry analysis of phytoplankton cultures and natural samples. Cytometry A 85(11):962–968.  https://doi.org/10.1002/cyto.a.22517 CrossRefPubMedGoogle Scholar
  35. 35.
    Shtaida N, Khozin-Goldberg I, Solovchenko A et al (2014) Downregulation of a putative plastid PDC E1α subunit impairs photosynthetic activity and triacylglycerol accumulation in nitrogen-starved photoautotrophic Chlamydomonas reinhardtii. J Exp Bot 65(22):6563–6576.  https://doi.org/10.1093/jxb/eru374 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tourasse NJ, Shtaida N, Khozin-Goldberg I et al (2015) The complete mitochondrial genome sequence of the green microalga Lobosphaera (Parietochloris) incisa reveals a new type of palindromic repetitive repeat. BMC Genomics 16:580.  https://doi.org/10.1186/s12864-015-1792-x CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Hamilton ML, Warwick J, Terry A et al (2015) Towards the industrial production of omega-3 long chain polyunsaturated fatty acids from a genetically modified diatom Phaeodactylum tricornutum. PLoS One 10(12):e0144054.  https://doi.org/10.1371/journal.pone.0144054 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Popko J, Herrfurth C, Feussner K et al (2016) Metabolome analysis reveals betaine lipids as major source for triglyceride formation, and the accumulation of sedoheptulose during nitrogen-starvation of Phaeodactylum tricornutum. PLoS One 11(10):e0164673.  https://doi.org/10.1371/journal.pone.0164673 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Tourasse NJ, Choquet Y, Vallon O (2013) PPR proteins of green algae. RNA Biol 10(9):1526–1542. PMC3858436CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Wannathong T, Waterhouse JC, Young REB et al (2016) New tools for chloroplast genetic engineering allow the synthesis of human growth hormone in the green alga Chlamydomonas reinhardtii. Appl Microbiol Biotechnol 100(12):5467–5477.  https://doi.org/10.1007/s00253-016-7354-6 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Zorin B, Grundman O, Khozin-Goldberg I et al (2014) Development of a nuclear transformation system for oleaginous green alga Lobosphaera (Parietochloris) incisa and genetic complementation of a mutant strain, deficient in arachidonic acid biosynthesis. PLoS One 9(8):e105223.  https://doi.org/10.1371/journal.pone.0105223 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Pal D, Khozin-Goldberg I, Didi-Cohen S et al (2013) Growth, lipid production and metabolic adjustments in the euryhaline eustigmatophyte Nannochloropsis oceanica CCALA 804 in response to osmotic downshift. Appl Microbiol Biotechnol 97(18):8291–8306.  https://doi.org/10.1007/s00253-013-5092-6 CrossRefPubMedGoogle Scholar
  43. 43.
    Bonente G, Ballottari M, Truong TB (2011a) Analysis of LhcSR3, a protein essential for feedback de-excitation in the green alga Chlamydomonas reinhardtii. PLoS Biol 9(1):e1000577.  https://doi.org/10.1371/journal.pbio.1000577 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Day A, Goldschmidt-Clermont MP (2011) The chloroplast transformation toolbox: selectable markers and marker removal. Plant Biotechnol J 9(5):540–553.  https://doi.org/10.1111/j.1467-7652.2011.00604.x CrossRefPubMedGoogle Scholar
  45. 45.
    Bonente G, Pippa S, Castellano S et al (2011b) Acclimation of Chlamydomonas reinhardtii to different growth irradiances. J Biol Chem 287(8):5833–5847.  https://doi.org/10.1074/jbc.M111.304279 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Petroutsos D, Busch A, Janssen I et al (2011) The chloroplast calcium sensor cas is required for photoacclimation in Chlamydomonas reinhardtii. Plant Cell 23(8):2950–2963.  https://doi.org/10.1105/tpc.111.087973 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    La Russa M, Bogen C, Uhmeyer A et al (2012) Functional analysis of three type-2 DGAT homologue genes for triacylglycerol production in the green microalga Chlamydomonas reinhardtii. J Biotechnol 162(1):13–20.  https://doi.org/10.1016/j.jbiotec.2012.04.006 CrossRefPubMedGoogle Scholar
  48. 48.
    Della Sala G, Hochmuth T, Costantino V et al (2013) Polyketide genes in the marine sponge Plakortis simplex: a new group of mono-modular type-i polyketide synthases from sponge symbionts. Environ Microbiol Rep 5:809–818.  https://doi.org/10.1111/1758-2229.12081 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ueoka R, Uria AR, Reite S et al (2015) Metabolic and evolutionary origin of actin-binding polyketides from diverse organisms. Nat Chem Biol 11:705–712.  https://doi.org/10.1038/nCHeMBIO.1870 CrossRefPubMedGoogle Scholar
  50. 50.
    Wang X, Tolba E, Schröder HC et al (2014) Effect of bioglass on growth and biomineralization of SaOS-2 cells in hydrogel after 3D cell bioprinting. PLoS One 9(11):e112497.  https://doi.org/10.1371/journal.pone.0112497 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Sinisi A, Calcinai B, Cerrano C et al (2013a) Isoswinholide B and swinholide K, potently cytotoxic dimeric macrolides from Theonella swinhoei. Bioorg Med Chem 21(17):5332–5338.  https://doi.org/10.1016/j.bmc.2013.06.015 CrossRefPubMedGoogle Scholar
  52. 52.
    Sinisi A, Calcinai B, Cerrano C et al (2013b) New Tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei. Beilstein J Org Chem 9:1643–1651.  https://doi.org/10.3762/bjoc.9.188 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    He F, Mai LH, Longeon A et al (2015) Novel adociaquinone derivatives from the indonesian sponge Xestospongia sp. Mar Drugs 13(5):2617–2628.  https://doi.org/10.3390/md13052617 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Chianese G, Sepe V, Limongelli V et al (2014) Incisterols, highly degraded marine sterols, are a new chemotype of PXR agonists. Steroids 83:80–85.  https://doi.org/10.1016/j.steroids.2014.02.003 CrossRefPubMedGoogle Scholar
  55. 55.
    Carstens BB, Rosengren KJ, Gunasekera S et al (2015) Isolation, characterization, and synthesis of the barrettides: disulfide-containing peptides from the marine sponge Geodia barretti. J Nat Prod 78(8):1886–1893.  https://doi.org/10.1021/acs.jnatprod.5b00210 CrossRefPubMedGoogle Scholar
  56. 56.
    Imperatore C, D’Aniello F, Aiello A et al (2014) Phallusiasterols A and B: two new sulfated sterols from the Mediterranean tunicate Phallusia fumigata and their effects as modulators of the PXR receptor. Mar Drugs 12(4):2066–2078.  https://doi.org/10.3390/md12042066 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Imperatore C, Senese M, Aiello A et al (2016) Phallusiasterol C, a new disulfated steroid from the Mediterranean tunicate Phallusia fumigate. Mar Drugs 4(6):117.  https://doi.org/10.3390/md14060117 CrossRefGoogle Scholar
  58. 58.
    Menna M, Aiello A, D’Aniello F et al (2013) Conithiaquinones A and B, tetracyclic cytotoxic meroterpenes from the Mediterranean ascidian Aplidium conicum. Eur J Org Chem 2013(16):3241–3246.  https://doi.org/10.1002/ejoc.201300260 CrossRefGoogle Scholar
  59. 59.
    Sabirova JS, Haddouche R, Van Bogaert IN et al (2011) The ‘LipoYeasts’ project: using the oleaginous yeast Yarrowia lipolytica in combination with specific bacterial genes for the bioconversion of lipids, fats and oils into high-value products. Microb Biotechnol 4:47–54.  https://doi.org/10.1111/j.1751-7915.2010.00187.x CrossRefPubMedGoogle Scholar
  60. 60.
    Beopoulos A, Cescut J, Haddouche R et al (2009) Yarrowia lipolytica as a model for bio-oil production. Prog Lipid Res 48:375–387.  https://doi.org/10.1016/j.plipres.2009.08.005 CrossRefPubMedGoogle Scholar
  61. 61.
    Kube M, Chernikova TN, Al-Ramahi Y et al (2013) Genome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica. Nat Commun 4:2156.  https://doi.org/10.1038/ncomms3156 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Leis B, Heinze S, Angelov A et al (2015) Functional screening of hydrolytic activities reveals an extremely thermostable cellulase from a deep-sea archaeon. Front Bioeng Biotechnol 3:95.  https://doi.org/10.3389/fbioe.2015.00095 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Messina E, Sorokin DY, Ilya VK et al (2016) Complete genome sequence of ‘halanaeroarchaeum sulfurireducens’ M27-SA2, a sulfur-reducing and acetate-oxidizing haloarchaeon from the deep-sea hypersaline anoxic lake Medee. Stand Genomic Sci 11:35.  https://doi.org/10.1186/s40793-016-0155-9 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Thies S, Rausch SC, Kovacic F et al (2016) Metagenomic discovery of novel enzymes and biosurfactants in a slaughterhouse biofilm microbial community. Sci Rep 6:27035.  https://doi.org/10.1038/srep27035 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Zapata-Pérez R, García-Saura AG, Jebbar M et al (2016) Combined whole-cell high-throughput functional screening for identification of new nicotinamidases/pyrazinamidases in metagenomic/polygenomic libraries. Front Microbiol 7:1915.  https://doi.org/10.3389/fmicb.2016.01915 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Thomas F, Lundqvist LCE, Jam M et al (2013) Comparative characterization of two marine alginate lyases from Zobellia galactanivorans reveals distinct modes of action and exquisite adaptation to their natural substrate. J Biol Chem 288(32):23021–23037.  https://doi.org/10.1074/jbc.M113.467217 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Genicot SM, Groisillier A, Rogniaux H et al (2014) Discovery of a novel iota carrageenan sulfatase isolated from the marine bacterium Pseudoalteromonas carrageenovora. Front Chem 2:67.  https://doi.org/10.3389/fchem.2014.00067 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Hodnik Ž, Tomašić T, Mašič L et al (2013) Novel state-dependent voltage-gated sodium channel modulators, based on marine alkaloids from Agelas sponges. J Med Chem 70:154–164.  https://doi.org/10.1016/j.ejmech.2013.07.034 CrossRefGoogle Scholar
  69. 69.
    Mencarelli A, D’Amore C, Renga B et al (2013) Solomonsterol A, a marine pregnane-x-receptor agonist, attenuates inflammation and immune dysfunction in a mouse model of arthritis. Mar Drugs 12(1):36–53.  https://doi.org/10.3390/md12010036 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Rodríguez AA, Salceda E, Garateix AG et al (2014) A novel sea anemone peptide that inhibits acid-sensing ion channels. Peptides 53:3–12.  https://doi.org/10.1016/j.peptides.2013.06.003 CrossRefPubMedGoogle Scholar
  71. 71.
    Zidar N, Montalvão S, Hodnik Ž et al (2014) Antimicrobial activity of the marine alkaloids, clathrodin and oroidin, and their synthetic analogues. Mar Drugs 12(2):940–963.  https://doi.org/10.3390/md12020940 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Majik M, Tilvi S, Parvatkar P (2014) Recent developments towards the synthesis of varitriol: an antitumour agent from marine derived fungus Emericella Variecolor. Curr Org Synth 11(2):268–287.  https://doi.org/10.2174/1570179410666131124134200 CrossRefGoogle Scholar
  73. 73.
    Sepe V, Di Leva FS, D’Amore C et al (2014) Marine and semi-synthetic hydroxysteroids as new scaffolds for pregnane x receptor modulation. Mar Drugs 12(6):3091–3115.  https://doi.org/10.3390/md12063091 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Sepe V, Ummarino R, D’Auria MV et al (2011) Total synthesis and pharmacological characterization of solomonsterol a, a potent marine pregnane-x-receptor agonist endowed with anti-inflammatory activity. J Med Chem 54(13):4590–4599.  https://doi.org/10.1021/jm200241s CrossRefPubMedGoogle Scholar
  75. 75.
    Žula A, Kikelj D, Ilaš J (2014) A convenient strategy for synthesizing the Agelas alkaloids clathrodin, oroidin, and hymenidin and their (un)saturated linker analogs. Tetrahedron Lett 55:3999–4001.  https://doi.org/10.1016/j.tetlet.2014.05.087 CrossRefGoogle Scholar
  76. 76.
    Fernández JJ, Daranas AH, Norte Martín M et al (2011) New polyether triterpenoids from Laurencia viridis and their biological evaluation. Mar Drugs 9(11):2220–2235.  https://doi.org/10.3390/md9112220 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Leirós M, Alonso E, Sanchez JA et al (2013) Mitigation of ROS insults by Streptomyces secondary metabolites in primary cortical neurons. ACS Chem Neurosci 5(1):71–80.  https://doi.org/10.1021/cn4001878 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Leirós M, Jon AS, Alonso E et al (2014) Spongionella secondary metabolites protect mitochondrial function in cortical neurons against oxidative stress. Mar Drugs 12(2):700–718.  https://doi.org/10.3390/md12020700 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Fondi M, de Pascale D, Tutino ML et al (2014) Draft genomes of three Antarctic Psychrobacter strains producing antimicrobial compounds against Burkholderia cepacia complex, opportunistic human pathogens. Mar Genomics 13:37–38.  https://doi.org/10.1016/j.margen.2013.12.009 CrossRefPubMedGoogle Scholar
  80. 80.
    Kennedy J, Flemer B, Jackson SA et al (2014) Evidence of a putative deep sea specific microbiome in marine sponges. PLoS One 9(3):e91092.  https://doi.org/10.1371/journal.pone.0091092 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Maida I, Fondi M, Papaleo MC et al (2014) Phenotypic and genomic characterization of the Antarctic bacterium Gillisia sp. CAL575, a producer of antimicrobial compounds. Extremophiles 18(1):35–49CrossRefPubMedGoogle Scholar
  82. 82.
    Tedesco P, Maida I, Esposito FP et al (2016) Antimicrobial activity of monoramnholipids produced by bacterial strains isolated from the Ross Sea (Antarctica). Mar Drugs 14(5):83.  https://doi.org/10.3390/md14050083 CrossRefPubMedCentralGoogle Scholar
  83. 83.
    Gnavi G, Esposito FP, Festa C et al (2016) The antimicrobial potential of algicolous marine fungi for counteracting multidrug-resistant bacteria: phylogenetic diversity and chemical profiling. Res Microbiol 167(6):492–500.  https://doi.org/10.1016/j.resmic.2016.04.009 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Lauritano C, Andersen JH, Hansen E et al (2016) Bioactivity screening of microalgae for antioxidant, anti-inflammatory, anticancer, anti-diabetes, and antibacterial activities. Front Mar Sci 3:68.  https://doi.org/10.3389/fmars.2016.00068 CrossRefGoogle Scholar
  85. 85.
    Pedro F (2016) Enzymes in fish and seafood processing. Front Bioeng Biotechnol 4:59.  https://doi.org/10.3389/fbioe.2016.00059 CrossRefGoogle Scholar
  86. 86.
    Ferrer M, Bargiela R, Martínez-Martínez M et al (2016) Biodiversity for biocatalysis: a review of the α/β-hydrolase fold superfamily of esterases-lipases discovered in metagenomes. Biocatal Biotransformation 33(5–6):235–249.  https://doi.org/10.3109/10242422.2016.1151416 CrossRefGoogle Scholar
  87. 87.
    Levinson W (2010) Review of medical microbiology and immunology, 11th edn. McGraw-Hill, New YorkGoogle Scholar
  88. 88.
    Salyers AA, Whitt DD (2002) Bacterial pathogenesis: a molecular approach, 2nd edn. ASM Press, Washington, DCGoogle Scholar
  89. 89.
    Pietrocola G, Nobile G, Gianotti V et al (2016) Molecular interactions of human plasminogen with fibronectin-binding protein b (fnbpb), a fibrinogen/fibronectin-binding protein from Staphylococcus aureus. J Biol Chem 291(35):18148–18162.  https://doi.org/10.1074/jbc.M116.731125 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Gumeni S, Ioannis TP (2016) Cross talk of proteostasis and mitostasis in cellular homeodynamics, ageing, and disease. Oxidative Med Cell Longev 2016:4587691.  https://doi.org/10.1155/2016/4587691 CrossRefGoogle Scholar
  91. 91.
    Querellou J, Borresen T, Boyen C et al (2010) Marine biotechnology: a new vision and strategy for Europe. Marine Board ESF Position Pap 15:1–96Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biotechnology Laboratory, Department of Integrative Marine EcologyStazione Zoologica Anton DohrnNaplesItaly

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