Skip to main content

Microbial and Functional Biodiversity Patterns in Sponges that Accumulate Bromopyrrole Alkaloids Suggest Horizontal Gene Transfer of Halogenase Genes


Marine sponge holobionts harbor complex microbial communities whose members may be the true producers of secondary metabolites accumulated by sponges. Bromopyrrole alkaloids constitute a typical class of secondary metabolites isolated from sponges that very often display biological activities. Bromine incorporation into secondary metabolites can be catalyzed by either halogenases or haloperoxidases. The diversity of the metagenomes of sponge holobiont species containing bromopyrrole alkaloids (Agelas spp. and Tedania brasiliensis) as well as holobionts devoid of bromopyrrole alkaloids spanning in a vast biogeographic region (approx. Seven thousand km) was studied. The origin and specificity of the detected halogenases was also investigated. The holobionts Agelas spp. and T. brasiliensis did not share microbial halogenases, suggesting a species-specific pattern. Bacteria of diverse phylogenetic origins encoding halogenase genes were found to be more abundant in bromopyrrole-containing sponges. The sponge holobionts (e.g., Agelas spp.) with the greatest number of sequences related to clustered, interspaced, short, palindromic repeats (CRISPRs) exhibited the fewest phage halogenases, suggesting a possible mechanism of protection from phage infection by the sponge host. This study highlights the potential of phages to transport halogenases horizontally across host sponges, particularly in more permissive holobiont hosts, such as Tedania spp.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. 1.

    Li CW, Chen JY, Hua TE (1998) Precambrian sponges with cellular structures. Science 279:879–882

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    Love GD, Grosjean E, Stalvies C, Fike DA, Grotzinger JP, Bradley AS, Kelly AE, Bhatia M, Meredith W, Snape CE, Bowring SA, Condon DJ, Summons RE (2009) Fossil steroids record the appearance of Demospongiae during the Cryogenian period. Nature 457:718–721.

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    Simion P, Philippe H, Baurain D, Jager M, Richter DJ, Di Franco A, Roure B, Satoh N, Queinnec E, Ereskovsky A, Lapebie P, Corre E, Delsuc F, King N, Worheide G, Manuel M (2017) A large and consistent phylogenomic dataset supports sponges as the sister group to all other animals. Curr Biol 27:958–967.

    Article  PubMed  CAS  Google Scholar 

  4. 4.

    Hooper JNA, van Soest RWM (2002) Systema Porifera: a guide to the classification of sponges. Kluwer Academic/ Plenum Publishers, New York

    Book  Google Scholar 

  5. 5.

    Moura RL, Amado-Filho GM, Moraes FC, Brasileiro PS, Salomon PS, Mahiques MM, Bastos AC, Almeida MG, Silva Jr JM, Araujo BF, Brito FP, Rangel TP, Oliveira BC, Bahia RG, Paranhos RP, Dias RJ, Siegle E, Figueiredo Jr AG, Pereira RC, Leal CV, Hajdu E, Asp NE, Gregoracci GB, Neumann-Leitao S, Yager PL, Francini-Filho RB, Froes A, Campeao M, Silva BS, Moreira AP, Oliveira L, Soares AC, Araujo L, Oliveira NL, Teixeira JB, Valle RA, Thompson CC, Rezende CE, Thompson FL (2016) An extensive reef system at the Amazon River mouth. Sci Adv 2:e1501252.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. 6.

    de Goeij JM, van Oevelen D, Vermeij MJ, Osinga R, Middelburg JJ, de Goeij AF, Admiraal W (2013) Surviving in a marine desert: the sponge loop retains resources within coral reefs. Science 342:108–110.

    Article  PubMed  CAS  Google Scholar 

  7. 7.

    Silveira CB, Silva-Lima AW, Francini-Filho RB, Marques JS, Almeida MG, Thompson CC, Rezende CE, Paranhos R, Moura RL, Salomon PS, Thompson FL (2015) Microbial and sponge loops modify fish production in phase-shifting coral reefs. Environ Microbiol 17:3832–3846.

    Article  PubMed  CAS  Google Scholar 

  8. 8.

    Webster NS (2017) Conceptual and methodological advances for holobiont research. Environ Microbiol Rep 9:30–32.

    Article  PubMed  Google Scholar 

  9. 9.

    Taylor MW, Radax R, Steger D, Wagner M (2007) Sponge-associated microorganisms: evolution, ecology, and biotechnological potential. Microbiol Mol Biol Rev 71:295–347.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. 10.

    Hentschel U, Piel J, Degnan SM, Taylor MW (2012) Genomic insights into the marine sponge microbiome. Nat Rev Microbiol 10:641–654.

    Article  PubMed  CAS  Google Scholar 

  11. 11.

    Rohwer F, Seguritan V, Azam F, Knowlton N (2002) Diversity and distribution of coral-associated bacteria. Mar Ecol Prog Ser 243:1–10

    Article  Google Scholar 

  12. 12.

    Webster NS, Thomas T (2016) The sponge hologenome. mBio 7.

  13. 13.

    Rosenberg E, Zilber-Rosenberg I (2016) Microbes drive evolution of animals and plants: the hologenome concept. mBio 7:e01395.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. 14.

    Paul VJ, Puglisi MP, Ritson-Williams R (2006) Marine chemical ecology. Nat Prod Rep 23:153–180.

    Article  PubMed  CAS  Google Scholar 

  15. 15.

    Thomas T, Rusch D, DeMaere MZ, Yung PY, Lewis M, Halpern A, Heidelberg KB, Egan S, Steinberg PD, Kjelleberg S (2010) Functional genomic signatures of sponge bacteria reveal unique and shared features of symbiosis. ISME J 4:1557–1567.

    Article  PubMed  CAS  Google Scholar 

  16. 16.

    Maldonado M, Ribes M, van Duyl FC (2012) Nutrient fluxes through sponges: biology, budgets, and ecological implications. Adv Mar Biol 62. doi:

  17. 17.

    Stierle AC, Cardellina 2nd JH, Singleton FL (1988) A marine Micrococcus produces metabolites ascribed to the sponge Tedania ignis. Experientia 44:1021

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Elyakov GB, Kuznetsova T, Mikhailov VV, Maltsev II, Voinov VG, Fedoreyev SA (1991) Brominated diphenyl ethers from a marine bacterium associated with the sponge Dysidea sp. Experientia 47:632–633.

    Article  CAS  Google Scholar 

  19. 19.

    Unson MD, Faulkner DJ (1993) Cyanobacterial symbiont biosynthesis of chlorinated metabolites from Dysidea herbacea (Porifera). Experientia 49:349–353.

    Article  CAS  Google Scholar 

  20. 20.

    Oclarit JM, Okada H, Ohta S, Kaminura K, Yamaoka Y, Iizuka T, Miyashiro S, Ikegami S (1994) Anti-bacillus substance in the marine sponge, Hyatella species, produced by an associated Vibrio species bacterium. Microbios 78:7–16

    PubMed  CAS  Google Scholar 

  21. 21.

    Bewley CA, Holland ND, Faulkner DJ (1996) Two classes of metabolites from Theonella swinhoei are localized in distinct populations of bacterial symbionts. Experientia 52:716–722

    Article  PubMed  CAS  Google Scholar 

  22. 22.

    Schmidt EW, Carole AB, Faulkner DJ (1998) Theopalauamide, a bicyclic glycopeptide from filamentous bacterial symbionts of the lithistid sponge Theonella swinhoei from Palau and Mozambique. J Org Chem 63:1254–1258

    Article  CAS  Google Scholar 

  23. 23.

    Bewley CA, Faulkner DJ (1998) Lithistid sponges: star performers or hosts to the star. Angew Chem Int Ed Engl 37:2162–2178

    Article  PubMed  Google Scholar 

  24. 24.

    Piel J, Hui DQ, Wen GP, Butzke D, Platzer M, Fusetani N, Matsunaga S (2004) Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei. Proc Natl Acad Sci U S A 101:16222–16227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. 25.

    Freeman MF, Gurgui C, Helf MJ, Morinaka BI, Uria AR, Oldham NJ, Sahl HG, Matsunaga S, Piel J (2012) Metagenome mining reveals polytheonamides as posttranslationally modified ribosomal peptides. Science 338:387–390.

    Article  PubMed  CAS  Google Scholar 

  26. 26.

    Wilson MC, Mori T, Ruckert C, Uria AR, Helf MJ, Takada K, Gernert C, Steffens UA, Heycke N, Schmitt S, Rinke C, Helfrich EJ, Brachmann AO, Gurgui C, Wakimoto T, Kracht M, Crusemann M, Hentschel U, Abe I, Matsunaga S, Kalinowski J, Takeyama H, Piel J (2014) An environmental bacterial taxon with a large and distinct metabolic repertoire. Nature 506:58–62.

    Article  PubMed  CAS  Google Scholar 

  27. 27.

    Nicacio KJ, Ioca LP, Froes AM, Leomil L, Appolinario LR, Thompson CC, Thompson FL, Ferreira AG, Williams DE, Andersen RJ, Eustaquio AS, Berlinck RG (2017) Cultures of the marine bacterium Pseudovibrio denitrificans Ab134 produce bromotyrosine-derived alkaloids previously only isolated from marine sponges. J Nat Prod 80:235–240.

    Article  PubMed  CAS  Google Scholar 

  28. 28.

    Schmitt S, Tsai P, Bell J, Fromont J, Ilan M, Lindquist N, Perez T, Rodrigo A, Schupp PJ, Vacelet J, Webster N, Hentschel U, Taylor MW (2011) Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges. ISME J 6:564–576

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. 29.

    Thomas T, Moitinho-Silva L, Lurgi M, Bjork JR, Easson C, Astudillo-Garcia C, Olson JB, Erwin PM, Lopez-Legentil S, Luter H, Chaves-Fonnegra A, Costa R, Schupp PJ, Steindler L, Erpenbeck D, Gilbert J, Knight R, Ackermann G, Victor Lopez J, Taylor MW, Thacker RW, Montoya JM, Hentschel U, Webster NS (2016) Diversity, structure and convergent evolution of the global sponge microbiome. Nat Commun 7:11870.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. 30.

    Erwin PM, Pita L, Lopez-Legentil S, Turon X (2012) Stability of sponge-associated bacteria over large seasonal shifts in temperature and irradiance. Appl Environ Microbiol 78:7358–7368.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. 31.

    Hardoim CC, Costa R (2014) Temporal dynamics of prokaryotic communities in the marine sponge Sarcotragus spinosulus. Mol Ecol 23:3097–3112.

    Article  PubMed  CAS  Google Scholar 

  32. 32.

    Hill M, Hill A, Lopez N, Harriott O (2006) Sponge-specific bacterial symbionts in the Caribbean sponge, Chondrilla nucula (Demospongiae, Chondrosida). Mar Biol 148:1221–1230.

    Article  Google Scholar 

  33. 33.

    Kamke J, Taylor MW, Schmitt S (2010) Activity profiles for marine sponge-associated bacteria obtained by 16S rRNA vs 16S rRNA gene comparisons. ISME J 4:498–508.

    Article  PubMed  CAS  Google Scholar 

  34. 34.

    Kennedy J, Codling CE, Jones BV, Dobson ADW, Marchesi JR (2008) Diversity of microbes associated with the marine sponge, Haliclona simulans, isolated from Irish waters and identification of polyketide synthase genes from the sponge metagenome. Environ Microbiol 10:1888–1902.

    Article  PubMed  CAS  Google Scholar 

  35. 35.

    Liu M, Fan L, Zhong L, Kjelleberg S, Thomas T (2012) Metaproteogenomic analysis of a community of sponge symbionts. ISME J 6:1515–1525.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. 36.

    Moitinho-Silva L, Bayer K, Cannistraci CV, Giles EC, Ryu T, Seridi L, Ravasi T, Hentschel U (2014) Specificity and transcriptional activity of microbiota associated with low and high microbial abundance sponges from the Red Sea. Mol Ecol 23:1348–1363.

    Article  PubMed  CAS  Google Scholar 

  37. 37.

    Reveillaud J, Maignien L, Eren AM, Huber JA, Apprill A, Sogin ML, Vanreusel A (2014) Host-specificity among abundant and rare taxa in the sponge microbiome. ISME J:1–12.

  38. 38.

    White JR, Patel J, Ottesen A, Arce G, Blackwelder P, Lopez JV (2012) Pyrosequencing of bacterial symbionts within Axinella corrugata sponges: diversity and seasonal variability. PLoS One 7:e38204.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. 39.

    Karlinska-Batres K, Worheide G (2013) Microbial diversity in the coralline sponge Vaceletia crypta. Antonie Van Leeuwenhoek 103:1041–1056.

    Article  PubMed  CAS  Google Scholar 

  40. 40.

    Friedrich AB, Fischer I, Proksch P, Hacker J, Hentschel U (2001) Temporal variation of the microbial community associated with the mediterranean sponge Aplysina aerophoba. FEMS Microbiol Ecol 38:105–113

    Article  CAS  Google Scholar 

  41. 41.

    Giles EC, Kamke J, Moitinho-Silva L, Taylor MW, Hentschel U, Ravasi T, Schmitt S (2013) Bacterial community profiles in low microbial abundance sponges. FEMS Microbiol Ecol 83:232–241.

    Article  PubMed  CAS  Google Scholar 

  42. 42.

    Hentschel U, Hopke J, Horn M, Friedrich AB, Wagner M, Hacker J, Moore BS (2002) Molecular evidence for a uniform microbial community in sponges from different oceans. Appl Environ Microbiol 68:4431–4440.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. 43.

    Trindade-Silva AE, Rua C, Silva GGZ, Dutilh BE, Moreira APB, Edwards RA, Hajdu E, Lobo-Hajdu G, Vasconcelos AT, Berlinck RGS, Thompson FL (2012) Taxonomic and functional microbial signatures of the endemic marine sponge Arenosclera brasiliensis. PLoS One 7:e39905

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. 44.

    Rua CP, Gregoracci GB, Santos EO, Soares AC, Francini-Filho RB, Thompson F (2015) Potential metabolic strategies of widely distributed holobionts in the oceanic archipelago of St Peter and St Paul (Brazil). FEMS Microbiol Ecol 91. doi:

  45. 45.

    Scala F, Fattorusso E, Menna M, Taglialatela-Scafati O, Tierney M, Kaiser M, Tasdemir D (2010) Bromopyrrole alkaloids as lead compounds against protozoan parasites. Mar Drugs 8:2162–2174.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. 46.

    da Silva FR, Tessis AC, Ferreira PF, Rangel LP, Garcia-Gomes AS, Pereira FR, Berlinck RG, Muricy G, Ferreira-Pereira A (2011) Oroidin inhibits the activity of the multidrug resistance target Pdr5p from yeast plasma membranes. J Nat Prod 74:279–282.

    Article  PubMed  CAS  Google Scholar 

  47. 47.

    Berlinck RGS, Parra LLL, Hajdu E, Ferreira AG, Tempone AG (2015) Combinatorial biosynthesis by the sponge Tedania brasiliensis optimizes the anti-parasitic activity of bromopyrrole alkaloids. Planta Med 81:P35.

    Article  Google Scholar 

  48. 48.

    Agarwal V, Miles ZD, Winter JM, Eustaquio AS, El Gamal AA, Moore BS (2017) Enzymatic halogenation and dehalogenation reactions: pervasive and mechanistically diverse. Chem Rev.

  49. 49.

    Yasuda T, Araki A, Kubota T, Ito J, Mikami Y, Fromont J, Kobayashi J (2009) Bromopyrrole alkaloids from marine sponges of the genus Agelas. J Nat Prod 72:488–491.

    Article  PubMed  CAS  Google Scholar 

  50. 50.

    Tanaka N, Kusama T, Kashiwada Y, Kobayashi J (2016) Bromopyrrole alkaloids from okinawan marine sponges Agelas spp. Chem Pharm Bull 64:691–694.

    Article  PubMed  CAS  Google Scholar 

  51. 51.

    Weigold P, El-Hadidi M, Ruecker A, Huson DH, Scholten T, Jochmann M, Kappler A, Behrens S (2016) A metagenomic-based survey of microbial (de)halogenation potential in a German forest soil. Sci Rep 6:28958.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. 52.

    Bayer K, Scheuermayer M, Fieseler L, Hentschel U (2013) Genomic mining for novel FADH(2)-dependent halogenases in marine sponge-associated microbial consortia. Mar Biotechnol 15:63–72.

    Article  PubMed  CAS  Google Scholar 

  53. 53.

    Öztürk B, de Jaeger L, Smidt H, Sipkema D (2013) Culture-dependent and independent approaches for identifying novel halogenases encoded by Crambe crambe (marine sponge) microbiota. Sci Rep 3. doi:

  54. 54.

    Al-Mourabit A, Zancanella MA, Tilvi S, Romo D (2011) Biosynthesis, asymmetric synthesis, and pharmacology, including cellular targets, of the pyrrole-2-aminoimidazole marine alkaloids. Nat Prod Rep 28:1229–1260.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. 55.

    Wang X, Ma Z, Wang X, De S, Ma Y, Chen C (2014) Dimeric pyrrole-imidazole alkaloids: synthetic approaches and biosynthetic hypotheses. Chem Commun 50:8628–8639.

    Article  CAS  Google Scholar 

  56. 56.

    Schroif-Gregoire C, Travert N, Zaparucha A, Al-Mourabit A (2006) Direct access to marine pyrrole-2-aminoimidazoles, oroidin, and derivatives, via new acyl-1,2-dihydropyridin intermediates. Org Lett 8:2961–2964.

    Article  PubMed  CAS  Google Scholar 

  57. 57.

    Braekman JC, Daloze D, Stoller C, Van Soest RWM (1992) Chemotaxonomy of Agelas (Porifera: Demospongiae). Biochem Syst Ecol 20:417–431

    Article  CAS  Google Scholar 

  58. 58.

    Vergne C, Boury-Esnault N, Perez T, Martin MT, Adeline MT, Tran Huu Dau E, Al-Mourabit A (2006) Verpacamides A-D, a sequence of C11N5 diketopiperazines relating cyclo(Pro-Pro) to cyclo(Pro-Arg), from the marine sponge Axinella vaceleti: possible biogenetic precursors of pyrrole-2-aminoimidazole alkaloids. Org Lett 8:2421–2424.

    Article  PubMed  CAS  Google Scholar 

  59. 59.

    Stout EP, Wang YG, Romo D, Molinski TF (2012) Pyrrole aminoimidazole alkaloid metabiosynthesis with marine sponges Agelas conifera and Stylissa caribica. Angew Chem Int Ed Engl 51:4877–4881.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. 60.

    Chanas B, Pawlik JR, Lindelb T, Fenical W (1997) Chemical defense of the Caribbean sponge Agelas clathrodes (Schmidt). J Exp Mar Biol Ecol 208:185–196.

    Article  Google Scholar 

  61. 61.

    Wilson DM, Puyana M, Fenical W, Pawlik JR (1999) Chemical defense of the Caribbean reef sponge Axinella corrugata against predatory fishes. J Chem Ecol 25

  62. 62.

    Assmann M, Lichte E, Pawlik JR, Köck M (2000) Chemical defenses of the Caribbean sponges Agelas wiedenmayeri and Agelas conifera. Mar Ecol Prog Ser 207:255–262

    Article  CAS  Google Scholar 

  63. 63.

    Assmann M, van Soest RW, Kock M (2001) New antifeedant bromopyrrole alkaloid from the Caribbean sponge Stylissa caribica. J Nat Prod 64:1345–1347

    Article  PubMed  CAS  Google Scholar 

  64. 64.

    Lindel T, Hoffmann H, Hochgürtel M, Pawlik JR (2000) Structure–activity relationship of inhibition of fish feeding by sponge-derived and synthetic pyrrole–imidazole alkaloids. J Chem Ecol 26:1477–1496

    Article  CAS  Google Scholar 

  65. 65.

    Kelly SR, Jensen PR, Henkel TP, Fenical W, Pawlik JR (2003) Effects of Caribbean sponge extracts on bacterial attachment. Aquat Microb Ecol 31:175–182

    Article  Google Scholar 

  66. 66.

    Hertiani T, Edrada-Ebel R, Ortlepp S, van Soest RW, de Voogd NJ, Wray V, Hentschel U, Kozytska S, Muller WE, Proksch P (2010) From anti-fouling to biofilm inhibition: new cytotoxic secondary metabolites from two Indonesian Agelas sponges. Bioorg Med Chem 18:1297–1311.

    Article  PubMed  CAS  Google Scholar 

  67. 67.

    Haber M, Carbone M, Mollo E, Gavagnin M, Ilan M (2011) Chemical defense against predators and bacterial fouling in the Mediterranean sponges Axinella polypoides and A. verrucosa. Mar Ecol Prog Ser 422:113–122

    Article  CAS  Google Scholar 

  68. 68.

    Tsukamoto S, Kato H, Hirota H, Fusetani N (1996) Pseudoceratidine: a new antifouling spermidine derivate from the marine sponge Pseudoceratina purpurea. Tetrahedron Lett 37:1439–1440

    Article  CAS  Google Scholar 

  69. 69.

    D'Amato ME, Corach D (1997) Repetitive DNA sequences as an insight into Aeglidae (Crustacea, Anomura) evolution. Electrophoresis 18:1666–1671.

    Article  PubMed  CAS  Google Scholar 

  70. 70.

    Keegan KP, Trimble WL, Wilkening J, Wilke A, Harrison T, D'Souza M, Meyer F (2012) A platform-independent method for detecting errors in metagenomic sequencing data: DRISEE. PLoS Comput Biol 8:e1002541.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. 71.

    Meyer F, Paarmann D, D'Souza M, Olson R, Glass EM, Kubal M, Paczian T, Rodriguez A, Stevens R, Wilke A, Wilkening J, Edwards RA (2008) The metagenomics RAST server—a public resource for the automatic phylogenetic and functional analysis of metagenomes. BMC Bioinformatics 9.

  72. 72.

    Parks DH, Tyson GW, Hugenholtz P, Beiko RG (2014) STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics 30:3123–3124.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. 73.

    Eddy SR (2008) A probabilistic model of local sequence alignment that simplifies statistical significance estimation. PLoS Comput Biol 4:e1000069.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. 74.

    Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW, Hauser LJ (2010) Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics 11:119.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. 75.

    Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, Potter SC, Punta M, Qureshi M, Sangrador-Vegas A, Salazar GA, Tate J, Bateman A (2016) The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res 44:D279–D285.

    Article  PubMed  CAS  Google Scholar 

  76. 76.

    Laurenzi A, Hung LH, Samudrala R (2013) Structure prediction of partial-length protein sequences. Int J Mol Sci 14:14892–14907.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. 77.

    Roy A, Kucukural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5:725–738.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. 78.

    Zhang C, Freddolino PL, Zhang Y (2017) COFACTOR: improved protein function prediction by combining structure, sequence and protein-protein interaction information. Nucleic Acids Res.

  79. 79.

    Bourne DG, Morrow KM, Webster NS (2016) Insights into the coral microbiome: underpinning the health and resilience of reef ecosystems. Annu Rev Microbiol 70:317–340.

    Article  PubMed  CAS  Google Scholar 

  80. 80.

    Schmitt S, Hentschel U, Taylor MW (2011) Deep sequencing reveals diversity and community structure of complex microbiota in five Mediterranean sponges. Hydrobiologia 687:341–351

    Article  CAS  Google Scholar 

  81. 81.

    Freeman CJ, Easson CG, Baker DM (2014) Metabolic diversity and niche structure in sponges from the Miskito Cays, Honduras. PeerJ 2:e695.

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Esteves AI, Cullen A, Thomas T (2017) Competitive interactions between sponge-associated bacteria. FEMS Microbiol Ecol 93.

  83. 83.

    Louca S, Parfrey LW, Doebeli M (2016) Decoupling function and taxonomy in the global ocean microbiome. Science 353:1272–1277.

    Article  PubMed  CAS  Google Scholar 

  84. 84.

    Tasdemir D, Topaloglu B, Perozzo R, Brun R, O'Neill R, Carballeira NM, Zhang X, Tonge PJ, Linden A, Ruedi P (2007) Marine natural products from the Turkish sponge Agelas oroides that inhibit the enoyl reductases from Plasmodium falciparum, Mycobacterium tuberculosis and Escherichia coli. Bioorg Med Chem 15:6834–6845.

    Article  PubMed  CAS  Google Scholar 

  85. 85.

    Parra LLL, Bertonha AF, Severo IRM, Aguiar ACC, de Souza GE, Oliva G, Guido RVC, Grazzia N, Costa TR, Miguel DC, Gadelha FR, Ferreira AG, Hajdu E, Romo D, Berlinck RGS (2018) Isolation, derivative synthesis, and structure-activity relationships of antiparasitic bromopyrrole alkaloids from the marine sponge Tedania brasiliensis. J Nat Prod.

  86. 86.

    Fan L, Reynolds D, Liu M, Stark M, Kjelleberg S, Webster NS, Thomas T (2012) Functional equivalence and evolutionary convergence in complex communities of microbial sponge symbionts. Proc Natl Acad Sci U S A 109:E1878–E1887.

    Article  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Agarwal V, Blanton JM, Podell S, Taton A, Schorn MA, Busch J, Lin Z, Schmidt EW, Jensen PR, Paul VJ, Biggs JS, Golden JW, Allen EE, Moore BS (2017) Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges. Nat Chem Biol 13:537–543.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. 88.

    Matcher GF, Waterworth SC, Walmsley TA, Matsatsa T, Parker-Nance S, Davies-Coleman MT, Dorrington RA (2017) Keeping it in the family: coevolution of latrunculid sponges and their dominant bacterial symbionts. Microbiol Open 6.

  89. 89.

    Bhushan A, Peters EE, Piel J (2017) Entotheonella bacteria as source of sponge-derived natural products: opportunities for biotechnological production. Prog Mol Subcell Biol 55:291–314.

    Article  PubMed  Google Scholar 

  90. 90.

    Niemann H, Marmann A, Lin W, Proksch P (2015) Sponge derived bromotyrosines: structural diversity through natural combinatorial chemistry. Nat Prod Commun 10:219–231

    PubMed  Google Scholar 

  91. 91.

    Shaala LA, Youssef DT, Badr JM, Sulaiman M, Khedr A (2015) Bioactive secondary metabolites from the Red Sea marine verongid sponge Suberea species. Mar Drugs 13:1621–1631.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. 92.

    Nicholas GM, Newton GL, Fahey RC, Bewley CA (2001) Novel bromotyrosine alkaloids: inhibitors of mycothiol S-conjugate amidase. Org Lett 3:1543–1545

    Article  PubMed  CAS  Google Scholar 

  93. 93.

    Tian LW, Feng Y, Shimizu Y, Pfeifer TA, Wellington C, Hooper JN, Quinn RJ (2014) ApoE secretion modulating bromotyrosine derivative from the Australian marine sponge Callyspongia sp. Bioorg Med Chem Lett 24:3537–3540.

    Article  PubMed  CAS  Google Scholar 

  94. 94.

    de Oliveira MF, de Oliveira JH, Galetti FC, de Souza AO, Silva CL, Hajdu E, Peixinho S, Berlinck RG (2006) Antimycobacterial brominated metabolites from two species of marine sponges. Planta Med 72:437–441.

    Article  PubMed  CAS  Google Scholar 

Download references


We thank Karen J. Nicacio (PhD student at IQSC, USP) for help in the literature survey as well as the funding agencies CNPq, FAPERJ, CAPES, and FAPESP for financial support.


This work was supported by FAPERJ [CNE E-26/110.735/2013 to E.H.], CAPES [CIMAR 1986/2014 to E.H.] and FAPESP [BIOTA/BIOprospecTA grant 2013/50228-8 to R.G.S.B. and Post-Doctoral Scholarship 2014/17616- 7 to C.P.J.R.].

Author information



Corresponding authors

Correspondence to Roberto G. S. Berlinck or Fabiano L. Thompson.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic Supplementary Material


Most abundant phyla/classes of Bacteria and Archaea found in metagenomes (GIF 186 kb)


Distribution of sequences with assigned functions in categories of subsystems—level 1 (GIF 263 kb)

High Resolution Image (TIFF 5823 kb)

High Resolution Image (TIFF 2339 kb)


(DOCX 22 kb)


(DOCX 19 kb)


(DOCX 588 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rua, C.P.J., de Oliveira, L.S., Froes, A. et al. Microbial and Functional Biodiversity Patterns in Sponges that Accumulate Bromopyrrole Alkaloids Suggest Horizontal Gene Transfer of Halogenase Genes. Microb Ecol 76, 825–838 (2018).

Download citation


  • Halogenases
  • Sponges
  • Metagenomics
  • Holobiont
  • Bromopyrrole alkaloids
  • Horizontal gene transfer