Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts
Abstract
:1. Introduction
2. Compounds from Ascidians and Their Symbionts
2.1. Alkaloids
2.1.1. Alkaloids from Ascidians
Didemnidines
Meridianins
Herdmanines
2.1.2. Alkaloids from Ascidian-Associated Microbes
Ecteinascidins
Eusynstyelamides
Sesbanimides
LL-14I352 α and β
2.2. Polypeptides
2.2.1. Polypeptides from Ascidians
Vitilevuamide
Diazonamides
Chondromodulin-1 (ChM-1)
CS5931
2.2.2. Polypeptides from Acidian-Associated Microbes
Didemnins
Patellamides
2.3. Polyketides
2.3.1. Polyketides from Ascidians
Palmerolide A
Mandelalides
Phosphoeleganin
2.3.2. Polyketides from Ascidian-Associated Microbes
Patellazoles
Arenimycin
2.4. Other Types of Compounds from Ascidians and the Host-Associated Microbes
3. The Effects of the Interaction between Ascidian-Associated Microbes and Hosts on the Production of Natural Compounds
3.1. Proteobacteria
3.2. Cyanobacteria
3.3. Actinomycetes
3.4. Fungi
4. Concluding Remarks
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Hotta, K.; Mitsuhara, K.; Takahashi, H.; Inaba, K.; Oka, K.; Gojobori, T.; Ikeo, K. A web-based interactive developmental table for the ascidian Ciona intestinalis, including 3D real-image embryo reconstructions: I. From fertilized egg to hatching larva. Dev. Dyn. 2007, 236, 1790–1805. [Google Scholar] [CrossRef] [PubMed]
- Delsuc, F.; Brinkmann, H.; Chourrout, D.; Philippe, H. Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature 2006, 439, 965–968. [Google Scholar] [CrossRef] [PubMed]
- Matthysse, A.G.; Deschet, K.; Williams, M.; Marry, M.; White, A.R.; Smith, W.C. A functional cellulose synthase from ascidian epidermis. Proc. Natl. Acad. Sci. USA 2004, 101, 986–991. [Google Scholar] [CrossRef] [PubMed]
- Nakashima, K.; Yamada, L.; Satou, Y.; Azuma, J.; Satoh, N. The evolutionary origin of animal cellulose synthase. Dev. Genes Evol. 2004, 214, 81–88. [Google Scholar] [CrossRef] [PubMed]
- Bhattachan, P.; Dong, B. Origin and evolutionary implications of introns from analysis of cellulose synthase gene. J. Syst. Evol. 2017, 55, 142–148. [Google Scholar] [CrossRef]
- Shenkar, N.; Swalla, B.J. Global diversity of Ascidiacea. PloS ONE 2011, 6, e20657. [Google Scholar] [CrossRef] [PubMed]
- Tsagkogeorga, G.; Turon, X.; Galtier, N.; Douzery, E.J.; Delsuc, F. Accelerated evolutionary rate of housekeeping genes in tunicates. J. Mol. Evol. 2010, 71, 153–167. [Google Scholar] [CrossRef] [PubMed]
- Holland, L.Z. Tunicates. Curr. Biol. 2016, 26, R146–R152. [Google Scholar] [CrossRef]
- Rudali, G.; Menetrier, L. Action of geranyl-hydroquinone on different spontaneous and induced cancers in the mouse. Therapie 1967, 22, 895–904. [Google Scholar]
- Rousseau, J.; Segal, J.P. [Clinical trial of a radioprotective medicine: Geranyl-hydroquinone in radiotherapeutic treatments]. SEM Ther. 1967, 43, 470–476. [Google Scholar]
- DavMson, B.S. Ascidians: Producers of Amino Acid Derived Metabolites. Chem. Rev. 1993, 93, 1771–1791. [Google Scholar]
- Palanisamy, S.K.; Rajendran, N.M.; Marino, A. Natural Products Diversity of Marine Ascidians (Tunicates; Ascidiacea) and Successful Drugs in Clinical Development. Nat. Prod. Bioprospect. 2017, 7, 1–111. [Google Scholar] [CrossRef] [PubMed]
- Watters, D.J. Ascidian Toxins with Potential for Drug Development. Mar. Drugs 2018, 16, 162. [Google Scholar] [CrossRef] [PubMed]
- Blunt, J.W.; Carroll, A.R.; Copp, B.R.; Davis, R.A.; Keyzers, R.A.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep. 2018, 35, 8–53. [Google Scholar] [CrossRef] [PubMed]
- Blunt, J.W.; Copp, B.R.; Hu, W.-P.; Munro, M.H.G.; Northcote, P.T.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep. 2009, 26, 170. [Google Scholar] [CrossRef] [PubMed]
- Agrawal, S.; Acharya, D.; Adholeya, A.; Barrow, C.J.; Deshmukh, S.K. Nonribosomal Peptides from Marine Microbes and Their Antimicrobial and Anticancer Potential. Front. Pharm. 2017, 8, 828. [Google Scholar] [CrossRef] [PubMed]
- Blunt, J.W.; Copp, B.R.; Keyzers, R.A.; Munro, M.H.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep. 2015, 32, 116–211. [Google Scholar] [CrossRef]
- Horta, A.; Alves, C.; Pinteus, S.; Pedrosa, R. Phycotoxins Chemistry and Biochemistry, 2nd ed.; Botana, L.M., Alfonso, A., Eds.; John Wiley & Sons, Ltd.: West Sussex, UK, 2015; pp. 293–316. [Google Scholar]
- Dumollard, R.; Gazo, I.; Gomes, I.D.L.; Besnardeau, L.; McDougall, A. Ascidians: An Emerging Marine Model for Drug Discovery and Screening. Curr. Top. Med. Chem. 2017, 17, 2056–2066. [Google Scholar] [CrossRef]
- Jimenez, P.C.; Wilke, D.V.; Branco, P.C.; Bauermeister, A.; Rezende-Teixeira, P.; Gaudencio, S.P.; Costa-Lotufo, L.V. Enriching Cancer Pharmacology with Drugs of Marine Origin. Br. J. Pharmacol. 2019. [Google Scholar] [CrossRef]
- Crawford, J.M.; Clardy, J. Bacterial symbionts and natural products. Chem. Commun. 2011, 47, 7559–7566. [Google Scholar] [CrossRef]
- Schmidt, E.W. The secret to a successful relationship: Lasting chemistry between ascidians and their symbiotic bacteria. Invertebr. Biol. 2015, 134, 88–102. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.; Fu, C.; Wang, G. Microbial diversity associated with ascidians: A review of research methods and application. Symbiosis 2016, 71, 19–26. [Google Scholar] [CrossRef]
- Chen, L.; Hu, J.S.; Xu, J.L.; Shao, C.L.; Wang, G.Y. Biological and Chemical Diversity of Ascidian-Associated Microorganisms. Mar. drugs 2018, 16, 362. [Google Scholar] [CrossRef] [PubMed]
- Wang, G. Diversity and biotechnological potential of the sponge-associated microbial consortia. J. Ind. Microbiol. Biotechnol. 2006, 33, 545–551. [Google Scholar] [CrossRef]
- Newman, D.J. Developing natural product drugs: Supply problems and how they have been overcome. Pharmcol. Ther. 2016, 162, 1–9. [Google Scholar] [CrossRef]
- Franco, L.H.; Joffe, E.B.; Puricelli, L.; Tatian, M.; Seldes, A.M.; Palermo, J.A. Indole alkaloids from the tunicate Aplidium meridianum. J. Nat. Prod. 1998, 61, 1130–1132. [Google Scholar] [CrossRef]
- Davis, R.A.; Carroll, A.R.; Pierens, G.K.; Quinn, R.J. New lamellarin alkaloids from the australian ascidian, didemnum chartaceum. J. Nat. Prod. 1999, 62, 419–424. [Google Scholar] [CrossRef]
- Quesada, A.R.; Garcia Gravalos, M.D.; Fernandez Puentes, J.L. Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. Br. J. Cancer 1996, 74, 677–682. [Google Scholar] [CrossRef]
- Kluza, J.; Gallego, M.A.; Loyens, A.; Beauvillain, J.C.; Sousa-Faro, J.M.; Cuevas, C.; Marchetti, P.; Bailly, C. Cancer cell mitochondria are direct proapoptotic targets for the marine antitumor drug lamellarin D. Cancer Res. 2006, 66, 3177–3187. [Google Scholar] [CrossRef]
- Sakai, R.; Rinehart, K.L.; Guan, Y.; Wang, A.H. Additional antitumor ecteinascidins from a Caribbean tunicate: Crystal structures and activities in vivo. Proc. Natl. Acad. Sci. USA 1992, 89, 11456–11460. [Google Scholar] [CrossRef]
- Pommier, Y.; Kohlhagen, G.; Bailly, C.; Waring, M.; Mazumder, A.; Kohn, K.W. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry 1996, 35, 13303–13309. [Google Scholar] [CrossRef] [PubMed]
- Finlayson, R.; Pearce, A.N.; Page, M.J.; Kaiser, M.; Bourguet-Kondracki, M.L.; Harper, J.L.; Webb, V.L.; Copp, B.R. Didemnidines A and B, indole spermidine alkaloids from the New Zealand ascidian Didemnum sp. J. Nat. Prod. 2011, 74, 888–892. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Kaiser, M.; Copp, B.R. Investigation of indolglyoxamide and indolacetamide analogues of polyamines as antimalarial and antitrypanosomal agents. Mar. Drugs 2014, 12, 3138–3160. [Google Scholar] [CrossRef] [PubMed]
- Nunez-Pons, L.; Nieto, R.M.; Avila, C.; Jimenez, C.; Rodriguez, J. Mass spectrometry detection of minor new meridianins from the Antarctic colonial ascidians Aplidium falklandicum and Aplidium meridianum. J. Mass Spectrom. 2015, 50, 103–111. [Google Scholar] [CrossRef] [PubMed]
- Bharate, S.B.; Yadav, R.R.; Battula, S.; Vishwakarma, R.A. Meridianins: Marine-derived potent kinase inhibitors. Mini Rev. Med. Chem. 2012, 12, 618–631. [Google Scholar] [CrossRef] [PubMed]
- Park, N.S.; Park, Y.K.; Ramalingam, M.; Yadav, A.K.; Cho, H.R.; Hong, V.S.; More, K.N.; Bae, J.H.; Bishop-Bailey, D.; Kano, J.; et al. Meridianin C inhibits the growth of YD-10B human tongue cancer cells through macropinocytosis and the down-regulation of Dickkopf-related protein-3. J. Cell Mol. Med. 2018, 22, 5833–5846. [Google Scholar] [CrossRef] [PubMed]
- Li, J.L.; Xiao, B.; Park, M.; Yoo, E.S.; Shin, S.; Hong, J.; Chung, H.Y.; Kim, H.S.; Jung, J.H. PPAR-gamma agonistic metabolites from the ascidian Herdmania momus. J. Nat. Prod. 2012, 75, 2082–2087. [Google Scholar] [CrossRef]
- Li, J.L.; Han, S.C.; Yoo, E.S.; Shin, S.; Hong, J.; Cui, Z.; Li, H.; Jung, J.H. Anti-inflammatory amino acid derivatives from the ascidian Herdmania momus. J. Nat. Prod. 2011, 74, 1792–1797. [Google Scholar] [CrossRef]
- D’Incalci, M.; Galmarini, C.M. A review of trabectedin (ET-743): A unique mechanism of action. Mol. Cancer Ther. 2010, 9, 2157–2163. [Google Scholar] [CrossRef] [Green Version]
- Gordon, E.M.; Sankhala, K.K.; Chawla, N.; Chawla, S.P. Trabectedin for Soft Tissue Sarcoma: Current Status and Future Perspectives. Adv. Ther. 2016, 33, 1055–1071. [Google Scholar] [CrossRef] [Green Version]
- Hendriks, H.R.; Fiebig, H.H.; Giavazzi, R.; Langdon, S.P.; Jimeno, J.M.; Faircloth, G.T. High antitumour activity of ET743 against human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer. Ann. Oncol. 1999, 10, 1233–1240. [Google Scholar] [CrossRef] [PubMed]
- Tapiolas, D.M.; Bowden, B.F.; Abou-Mansour, E.; Willis, R.H.; Doyle, J.R.; Muirhead, A.N.; Liptrot, C.; Llewellyn, L.E.; Wolff, C.W.; Wright, A.D.; et al. Eusynstyelamides A, B, and C, nNOS inhibitors, from the ascidian Eusynstyela latericius. J. Nat. Prod. 2009, 72, 1115–1120. [Google Scholar] [CrossRef] [PubMed]
- Swersey, J.C.; Ireland, C.M.; Cornell, L.M.; Peterson, R.W. Eusynstyelamide, a highly modified dimer peptide from the ascidian Eusynstyela misakiensis. J. Nat. Prod. 1994, 57, 842–845. [Google Scholar] [CrossRef] [PubMed]
- Liberio, M.; Sadowski, M.; Nelson, C.; Davis, R. Identification of Eusynstyelamide B as a Potent Cell Cycle Inhibitor Following the Generation and Screening of an Ascidian-Derived Extract Library Using a Real Time Cell Analyzer. Mar. Drugs 2014, 12, 5222–5239. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Acebal, C.; Alcazar, R.; Canedo, L.M.; de la Calle, F.; Rodriguez, P.; Romero, F.; Fernandez Puentes, J.L. Two marine Agrobacterium producers of sesbanimide antibiotics. J. Antibiot. 1998, 51, 64–67. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.L.; Krakoff, I.H.; Newman, R.A. Isolation of sesbanimide from the seed of Sesbania vesicaria. Gen. Pharmcol. 1992, 23, 701–703. [Google Scholar] [CrossRef]
- Singh, M.P.; Menendez, A.T.; Petersen, P.J.; Ding, W.D.; Maiese, W.M.; Greenstein, M. Biological and mechanistic activities of phenazine antibiotics produced by culture LL-14I352. J. Antibiot. 1997, 50, 785–787. [Google Scholar] [CrossRef] [Green Version]
- Cheung, R.C.; Ng, T.B.; Wong, J.H. Marine Peptides: Bioactivities and Applications. Mar. Drugs 2015, 13, 4006–4043. [Google Scholar] [CrossRef]
- Gogineni, V.; Hamann, M.T. Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology. Biochim. Biophys. Acta Gen. Subj. 2018, 1862, 81–196. [Google Scholar] [CrossRef]
- Cruz-Monserrate, Z.; Vervoort, H.C.; Bai, R.; Newman, D.J.; Howell, S.B.; Los, G.; Mullaney, J.T.; Williams, M.D.; Pettit, G.R.; Fenical, W.; et al. Diazonamide A and a synthetic structural analog: Disruptive effects on mitosis and cellular microtubules and analysis of their interactions with tubulin. Mol. Pharmcol. 2003, 63, 1273–1280. [Google Scholar] [CrossRef] [Green Version]
- Su, S.; Xu, H.; Chen, X.; Qiao, G.; Farooqi, A.A.; Tian, Y.; Yuan, R.; Liu, X.; Li, C.; Li, X.; et al. CS5931, A Novel Marine Polypeptide, Inhibits Migration and Invasion of Cancer Cells Via Interacting with Enolase 1. Recent Pat. Anticancer Drug Discov. 2018, 13, 360–367. [Google Scholar] [CrossRef] [PubMed]
- Edler, M.C.; Fernandez, A.M.; Lassota, P.; Ireland, C.M.; Barrows, L.R. Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide, at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10. Biochem. Pharmcol. 2002, 63, 707–715. [Google Scholar] [CrossRef]
- Singh, R.; Sharma, M.; Joshi, P.; Rawat, D.S. Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med. Chem. 2008, 8, 603–617. [Google Scholar] [CrossRef] [PubMed]
- Ding, H.; DeRoy, P.L.; Perreault, C.; Larivee, A.; Siddiqui, A.; Caldwell, C.G.; Harran, S.; Harran, P.G. Electrolytic macrocyclizations: Scalable synthesis of a diazonamide-based drug development candidate. Angew. Chem. Int. Ed. Engl. 2015, 54, 4818–4822. [Google Scholar] [CrossRef] [PubMed]
- Newman, D.J.; Cragg, G.M. Current Status of Marine-Derived Compounds as Warheads in Anti-Tumor Drug Candidates. Mar. Drugs 2017, 15, 99. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mori, Y.; Hiraki, Y.; Shukunami, C.; Kakudo, S.; Shiokawa, M.; Kagoshima, M.; Mano, H.; Hakeda, Y.; Kurokawa, T.; Suzuki, F.; et al. Stimulation of osteoblast proliferation by the cartilage-derived growth promoting factors chondromodulin-I and -II. FEBS Lett. 1997, 406, 310–314. [Google Scholar] [CrossRef] [Green Version]
- Dou, X.; Li, X.; Yu, H.; Dong, B. Dual Roles of Ascidian Chondromodulin-1: Promoting Cell Proliferation Whilst Suppressing the Growth of Tumor Cells. Mar. Drugs 2018, 16, 59. [Google Scholar] [CrossRef] [Green Version]
- Zhao, J.; Wei, J.; Liu, M.; Xiao, L.; Wu, N.; Liu, G.; Huang, H.; Zhang, Y.; Zheng, L.; Lin, X. Cloning, characterization and expression of a cDNA encoding a granulin-like polypeptide in Ciona savignyi. Biochimie 2013, 95, 1611–1619. [Google Scholar] [CrossRef]
- Cheng, L.; Wang, C.; Liu, H.; Wang, F.; Zheng, L.; Zhao, J.; Chu, E.; Lin, X. A novel polypeptide extracted from Ciona savignyi induces apoptosis through a mitochondrial-mediated pathway in human colorectal carcinoma cells. Clin. Colorectal Cancer 2012, 11, 207–214. [Google Scholar] [CrossRef]
- Liu, G.; Liu, M.; Wei, J.; Huang, H.; Zhang, Y.; Zhao, J.; Xiao, L.; Wu, N.; Zheng, L.; Lin, X. CS5931, a novel polypeptide in Ciona savignyi, represses angiogenesis via inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Mar. Drugs 2014, 12, 1530–1544. [Google Scholar] [CrossRef] [Green Version]
- Rinehart, K.L., Jr.; Gloer, J.B.; Hughes, R.G., Jr.; Renis, H.E.; McGovren, J.P.; Swynenberg, E.B.; Stringfellow, D.A.; Kuentzel, S.L.; Li, L.H. Didemnins: Antiviral and antitumor depsipeptides from a caribbean tunicate. Science 1981, 212, 933–935. [Google Scholar] [CrossRef] [PubMed]
- Chun, H.G.; Davies, B.; Hoth, D.; Suffness, M.; Plowman, J.; Flora, K.; Grieshaber, C.; Leyland-Jones, B.; Didemnin, B. The first marine compound entering clinical trials as an antineoplastic agent. Investig. New Drugs 1986, 4, 279–284. [Google Scholar]
- Rinehart, K.L.; Kishore, V.; Bible, K.C.; Sakai, R.; Sullins, D.W.; Li, K.M. Didemnins and tunichlorin: Novel natural products from the marine tunicate Trididemnum solidum. J. Nat. Prod. 1988, 51, 1–21. [Google Scholar] [CrossRef] [PubMed]
- Fatima, I.; Kanwal, S.; Mahmood, T. Natural Products Mediated Targeting of Virally Infected Cancer. Dose Response 2019, 17. [Google Scholar] [CrossRef] [PubMed]
- Lichota, A.; Gwozdzinski, K. Anticancer Activity of Natural Compounds from Plant and Marine Environment. Int. J. Mol. Sci. 2018, 19, 3533. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kucuk, O.; Young, M.L.; Habermann, T.M.; Wolf, B.C.; Jimeno, J.; Cassileth, P.A. Phase II trail of didemnin B in previously treated non-Hodgkin’s lymphoma: An Eastern Cooperative Oncology Group (ECOG) Study. Am. J. Clin. Oncol. 2000, 23, 273–277. [Google Scholar] [CrossRef]
- Le Tourneau, C.; Raymond, E.; Faivre, S. Aplidine: A paradigm of how to handle the activity and toxicity of a novel marine anticancer poison. Curr. Pharm. Des. 2007, 13, 3427–3439. [Google Scholar] [CrossRef]
- Broggini, M.; Marchini, S.V.; Galliera, E.; Borsotti, P.; Taraboletti, G.; Erba, E.; Sironi, M.; Jimeno, J.; Faircloth, G.T.; Giavazzi, R.; et al. Aplidine, a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4. Leukemia 2003, 17, 52–59. [Google Scholar] [CrossRef] [Green Version]
- Degnan, B.M.; Hawkins, C.J.; Lavin, M.F.; McCaffrey, E.J.; Parry, D.L.; van den Brenk, A.L.; Watters, D.J. New cyclic peptides with cytotoxic activity from the ascidian Lissoclinum patella. J. Med. Chem. 1989, 32, 1349–1354. [Google Scholar] [CrossRef]
- Koehnke, J.; Bent, A.F.; Houssen, W.E.; Mann, G.; Jaspars, M.; Naismith, J.H. The structural biology of patellamide biosynthesis. Curr. Opin. Struct. Biol. 2014, 29, 112–121. [Google Scholar] [CrossRef] [Green Version]
- Amoutzias, G.D.; Chaliotis, A.; Mossialos, D. Discovery Strategies of Bioactive Compounds Synthesized by Nonribosomal Peptide Synthetases and Type-I Polyketide Synthases Derived from Marine Microbiomes. Mar. Drugs 2016, 14, 80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Imperatore, C.; Luciano, P.; Aiello, A.; Vitalone, R.; Irace, C.; Santamaria, R.; Li, J.; Guo, Y.W.; Menna, M. Structure and Configuration of Phosphoeleganin, a Protein Tyrosine Phosphatase 1B Inhibitor from the Mediterranean Ascidian Sidnyum elegans. J. Nat. Prod. 2016, 79, 1144–1148. [Google Scholar] [CrossRef] [PubMed]
- Noguez, J.H.; Diyabalanage, T.K.; Miyata, Y.; Xie, X.S.; Valeriote, F.A.; Amsler, C.D.; McClintock, J.B.; Baker, B.J. Palmerolide macrolides from the Antarctic tunicate Synoicum adareanum. Bioorg. Med. Chem. 2011, 19, 6608–6614. [Google Scholar] [CrossRef] [PubMed]
- Lisboa, M.P.; Jones, D.M.; Dudley, G.B. Formal synthesis of palmerolide A, featuring alkynogenic fragmentation and syn-selective vinylogous aldol chemistry. Org. Lett. 2013, 15, 886–889. [Google Scholar] [CrossRef]
- Sikorska, J.; Hau, A.M.; Anklin, C.; Parker-Nance, S.; Davies-Coleman, M.T.; Ishmael, J.E.; McPhail, K.L. Mandelalides A-D, cytotoxic macrolides from a new Lissoclinum species of South African tunicate. J. Org. Chem. 2012, 77, 6066–6075. [Google Scholar] [CrossRef] [Green Version]
- Nazari, M.; Serrill, J.D.; Wan, X.; Nguyen, M.H.; Anklin, C.; Gallegos, D.A.; Smith, A.B., 3rd; Ishmael, J.E.; McPhail, K.L. New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors. J. Med. Chem. 2017, 60, 7850–7862. [Google Scholar] [CrossRef]
- Richardson, A.D.; Aalbersberg, W.; Ireland, C.M. The patellazoles inhibit protein synthesis at nanomolar concentrations in human colon tumor cells. Anticancer Drugs 2005, 16, 533–541. [Google Scholar] [CrossRef]
- Asolkar, R.N.; Kirkland, T.N.; Jensen, P.R.; Fenical, W. Arenimycin, an antibiotic effective against rifampin- and methicillin-resistant Staphylococcus aureus from the marine actinomycete Salinispora arenicola. J. Antibiot. 2010, 63, 37–39. [Google Scholar] [CrossRef] [Green Version]
- Jakubiec-Krzesniak, K.; Rajnisz-Mateusiak, A.; Guspiel, A.; Ziemska, J.; Solecka, J. Secondary Metabolites of Actinomycetes and their Antibacterial, Antifungal and Antiviral Properties. Pol. J. Microbiol. 2018, 67, 259–272. [Google Scholar] [CrossRef] [Green Version]
- Carballo, J.L.; Naranjo, S. Environmental assessment of a large industrial marine complex based on a community of benthic filter-feeders. Mar. Pollut. Bull. 2002, 44, 605–610. [Google Scholar] [CrossRef]
- McFall-Ngai, M.; Hadfield, M.G.; Bosch, T.C.; Carey, H.V.; Domazet-Loso, T.; Douglas, A.E.; Dubilier, N.; Eberl, G.; Fukami, T.; Gilbert, S.F.; et al. Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl. Acad. Sci. USA 2013, 110, 3229–3236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Newman, D.J.; Hill, R.T. New drugs from marine microbes: The tide is turning. J. Ind. Microbiol. Biotechnol. 2006, 33, 539–544. [Google Scholar] [CrossRef] [PubMed]
- Arai, T.; Takahashi, K.; Nakahara, S.; Kubo, A. The structure of a novel antitumor antibiotic, saframycin A. Experientia 1980, 36, 1025–1027. [Google Scholar] [CrossRef] [PubMed]
- Piel, J. Bacterial symbionts: Prospects for the sustainable production of invertebrate-derived pharmaceuticals. Curr. Med. Chem. 2006, 13, 39–50. [Google Scholar] [CrossRef] [PubMed]
- Schofield, M.M.; Jain, S.; Porat, D.; Dick, G.J.; Sherman, D.H. Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743. Environ. Microbiol. 2015, 17, 3964–3975. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rath, C.M.; Janto, B.; Earl, J.; Ahmed, A.; Hu, F.Z.; Hiller, L.; Dahlgren, M.; Kreft, R.; Yu, F.; Wolff, J.J.; et al. Meta-omic characterization of the marine invertebrate microbial consortium that produces the chemotherapeutic natural product ET-743. ACS Chem. Biol. 2011, 6, 1244–1256. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morita, M.; Schmidt, E.W. Parallel lives of symbionts and hosts: Chemical mutualism in marine animals. Nat. Prod. Rep. 2018, 35, 357–378. [Google Scholar] [CrossRef]
- Nakabachi, A.; Ueoka, R.; Oshima, K.; Teta, R.; Mangoni, A.; Gurgui, M.; Oldham, N.J.; van Echten-Deckert, G.; Okamura, K.; Yamamoto, K.; et al. Defensive bacteriome symbiont with a drastically reduced genome. Curr. Biol. 2013, 23, 1478–1484. [Google Scholar] [CrossRef] [Green Version]
- Moran, N.A.; McCutcheon, J.P.; Nakabachi, A. Genomics and evolution of heritable bacterial symbionts. Annu. Rev. Genet. 2008, 42, 165–190. [Google Scholar] [CrossRef] [Green Version]
- Perez-Matos, A.E.; Rosado, W.; Govind, N.S. Bacterial diversity associated with the Caribbean tunicate Ecteinascidia turbinata. Antonie Leeuwenhoek 2007, 92, 155–164. [Google Scholar] [CrossRef]
- Cassier-Chauvat, C.; Dive, V.; Chauvat, F. Cyanobacteria: Photosynthetic factories combining biodiversity, radiation resistance, and genetics to facilitate drug discovery. Appl. Microbiol. Biotechnol. 2017, 101, 1359–1364. [Google Scholar] [CrossRef] [PubMed]
- Shimada, A.; Yano, N.; Kanai, S.; Ralph, A.L.; Maruyama, T. Molecular phylogenetic relationship between two symbiotic photo-oxygenic prokaryotes, Prochloron sp. and Synechocystis trididemn. Phycologia 2003, 42, 193–197. [Google Scholar] [CrossRef]
- Hirose, E. Ascidian photosymbiosis: Diversity of cyanobacterial transmission during embryogenesis. Genesis 2015, 53, 121–131. [Google Scholar] [CrossRef] [PubMed]
- Lewin, R.A. Prochlorophyta as a proposed new division of algae. Nature 1976, 261, 697–698. [Google Scholar] [CrossRef]
- Miller, S.R.; Augustine, S.; Olson, T.L.; Blankenship, R.E.; Selker, J.; Wood, A.M. Discovery of a free-living chlorophyll d-producing cyanobacterium with a hybrid proteobacterial/cyanobacterial small-subunit rRNA gene. Proc. Natl. Acad. Sci. USA 2005, 102, 850–855. [Google Scholar] [CrossRef] [Green Version]
- Kuhl, M.; Chen, M.; Ralph, P.J.; Schreiber, U.; Larkum, A.W. Ecology: A niche for cyanobacteria containing chlorophyll d. Nature 2005, 433, 820. [Google Scholar] [CrossRef]
- Hirosea, E. Pigmentation and acid storage in the tunic: Protective functions of the tunic cells in the tropical ascidian Phallusia nigra. Invertebr. Biol. 1999, 118, 414–422. [Google Scholar] [CrossRef]
- Lopez-Legentil, S.; Song, B.; Bosch, M.; Pawlik, J.R.; Turon, X. Cyanobacterial diversity and a new acaryochloris-like symbiont from Bahamian sea-squirts. PLoS ONE 2011, 6, e23938. [Google Scholar] [CrossRef] [Green Version]
- Tarjuelo I, I.; Posada, D.; Crandall, K.A.; Pascual, M.; Turon, X. Cryptic species of Clavelina (Ascidiacea) in two different habitats: Harbours and rocky littoral zones in the northwestern Mediterranean. Mar. Biol. 2001, 139, 455–462. [Google Scholar]
- Hirose, E.; Hirose, M.; Neilan, B.A. Localization of symbiotic cyanobacteria in the colonial ascidian Trididemnum miniatum (Didemnidae, Ascidiacea). Zool. Sci. 2006, 23, 435–442. [Google Scholar] [CrossRef]
- Alberte, R.S.; Cheng, L.; Lewin, R.A. Photosynthetic characteristics of Prochloron sp./ascidian symbioses. Mar. Biol. 1986, 90, 575–587. [Google Scholar] [CrossRef]
- Donia, M.S.; Fricke, W.F.; Partensky, F.; Cox, J.; Elshahawi, S.I.; White, J.R.; Phillippy, A.M.; Schatz, M.C.; Piel, J.; Haygood, M.G.; et al. Complex microbiome underlying secondary and primary metabolism in the tunicate-Prochloron symbiosis. Proc. Natl. Acad. Sci. USA 2011, 108, E1423–E1432. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, Q.; Dolganov, N.; Bjorkman, O.; Grossman, A.R. The high light-inducible polypeptides in Synechocystis PCC6803. Expression and function in high light. J. Biol. Chem. 2001, 276, 306–314. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dionisio-Sese, M.L.; Maruyama, T.; Miyachi, S. Photosynthesis of Prochloron as affected by environmental factors. Mar. Biotechnol. 2001, 3, 74–79. [Google Scholar] [CrossRef]
- Douglas, G.C.; Deborah, A.B.; Margaret, R.M.; Edward, J.C. Nitrogen in the Marine Environment, 2nd ed.; Elsevier Inc: Amsterdam, The Netherlands, 2008; pp. 1073–1095. [Google Scholar]
- Lesser, M.P.; Stochaj, W.R. Photoadaptation and Protection against Active Forms of Oxygen in the Symbiotic Procaryote Prochloron sp. and Its Ascidian Host. Appl. Environ. Microbiol. 1990, 56, 1530–1535. [Google Scholar]
- Comba, P.; Dovalil, N.; Gahan, L.R.; Hanson, G.R.; Westphal, M. Cyclic peptide marine metabolites and CuII. Dalton Trans. 2014, 43, 1935–1956. [Google Scholar] [CrossRef] [Green Version]
- Martins, J.; Vasconcelos, V. Cyanobactins from Cyanobacteria: Current Genetic and Chemical State of Knowledge. Mar. Drugs 2015, 13, 6910–6946. [Google Scholar] [CrossRef] [Green Version]
- Tel-or, E.; Huflejt, M.E.; Packer, L. Hydroperoxide metabolism in cyanobacteria. Arch. Biochem. Biophys. 1986, 246, 396–402. [Google Scholar] [CrossRef]
- Parry, D.L. Nitrogen assimilation in the symbiotic marine algae Prochloron spp. Mar. Biol. 1985, 87, 219–222. [Google Scholar] [CrossRef]
- Nakamura, H.; Kobayashi, J.; Hirata, Y. Separation of mycosporine-like amino acids in marine organisms using reversed-phase high-performance liquid chromatography. J. Chromatogr. A 1982, 250, 113–118. [Google Scholar] [CrossRef]
- Suh, H.J.; Lee, H.W.; Jung, J. Mycosporine glycine protects biological systems against photodynamic damage by quenching singlet oxygen with a high efficiency. Photochem. Photobiol. 2003, 78, 109–113. [Google Scholar] [CrossRef]
- Balskus, E.P.; Walsh, C.T. The genetic and molecular basis for sunscreen biosynthesis in cyanobacteria. Science 2010, 329, 1653–1656. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karsten, U.; Sawall, T.; West, J.; Wiencke, C. Ultraviolet sunscreen compounds in epiphytic red algae from mangroves. Hydrobiologia 2000, 432, 159–171. [Google Scholar] [CrossRef]
- Hirose, E.; Hirabayashi, S.; Hori, K.; Kasai, F.; Watanabe, M.M. UV protection in the photosymbiotic ascidian Didemnum molle inhabiting different depths. Zool. Sci. 2006, 23, 57–63. [Google Scholar] [CrossRef]
- Donia, M.S.; Fricke, W.F.; Ravel, J.; Schmidt, E.W. Variation in tropical reef symbiont metagenomes defined by secondary metabolism. PloS ONE 2011, 6, e17897. [Google Scholar] [CrossRef] [Green Version]
- Mendez-Perez, D.; Begemann, M.B.; Pfleger, B.F. Modular synthase-encoding gene involved in alpha-olefin biosynthesis in Synechococcus sp. strain PCC 7002. Appl. Environ. Microbiol. 2011, 77, 4264–4267. [Google Scholar] [CrossRef] [Green Version]
- Donia, M.S.; Ravel, J.; Schmidt, E.W. A global assembly line for cyanobactins. Nat. Chem. Biol. 2008, 4, 341–343. [Google Scholar] [CrossRef]
- Arnison, P.G.; Bibb, M.J.; Bierbaum, G.; Bowers, A.A.; Bugni, T.S.; Bulaj, G.; Camarero, J.A.; Campopiano, D.J.; Challis, G.L.; Clardy, J.; et al. Ribosomally synthesized and post-translationally modified peptide natural products: Overview and recommendations for a universal nomenclature. Nat. Prod. Rep. 2013, 30, 108–160. [Google Scholar] [CrossRef]
- Donia, M.S.; Hathaway, B.J.; Sudek, S.; Haygood, M.G.; Rosovitz, M.J.; Ravel, J.; Schmidt, E.W. Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nat. Chem. Biol. 2006, 2, 729–735. [Google Scholar] [CrossRef]
- Kwan, J.C.; Tianero, M.D.; Donia, M.S.; Wyche, T.P.; Bugni, T.S.; Schmidt, E.W. Host control of symbiont natural product chemistry in cryptic populations of the tunicate Lissoclinum patella. PloS ONE 2014, 9, e95850. [Google Scholar] [CrossRef]
- Schmidt, E.W.; Nelson, J.T.; Rasko, D.A.; Sudek, S.; Eisen, J.A.; Haygood, M.G.; Ravel, J. Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proc. Natl. Acad. Sci. USA 2005, 102, 7315–7320. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, Z.; Torres, J.P.; Tianero, M.D.; Kwan, J.C.; Schmidt, E.W. Origin of Chemical Diversity in Prochloron-Tunicate Symbiosis. Appl. Environ. Microbiol. 2016, 82, 3450–3460. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schnell, N.; Entian, K.D.; Schneider, U.; Gotz, F.; Zahner, H.; Kellner, R.; Jung, G. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature 1988, 333, 276–278. [Google Scholar] [CrossRef] [PubMed]
- Degnan, B.M.; Hawkins, C.J.; Lavin, M.F.; McCaffrey, E.J.; Parry, D.L.; Watters, D.J. Novel cytotoxic compounds from the ascidian Lissoclinum bistratum. J. Med. Chem. 1989, 32, 1354–1359. [Google Scholar] [CrossRef]
- Manivasagan, P.; Venkatesan, J.; Sivakumar, K.; Kim, S.K. Pharmaceutically active secondary metabolites of marine actinobacteria. Microbiol. Res. 2014, 169, 262–278. [Google Scholar] [CrossRef]
- Buedenbender, L.; Carroll, A.R.; Kurtböke, İ. Frontiers in Clinical Drug Research-Anti Infectives; Rahman, A.U., Ed.; Bentham Books: Sharjah, UAE, 2019; Volume 5, pp. 1–40. [Google Scholar]
- Socha, A.M.; Garcia, D.; Sheffer, R.; Rowley, D.C. Antibiotic bisanthraquinones produced by a streptomycete isolated from a cyanobacterium associated with Ecteinascidia turbinata. J. Nat. Prod. 2006, 69, 1070–1073. [Google Scholar] [CrossRef]
- Harunari, E.; Imada, C.; Igarashi, Y.; Fukuda, T.; Terahara, T.; Kobayashi, T. Hyaluromycin, a new hyaluronidase inhibitor of polyketide origin from marine Streptomyces sp. Mar. Drugs 2014, 12, 491–507. [Google Scholar] [CrossRef] [Green Version]
- Steinert, G.; Taylor, M.W.; Schupp, P.J. Diversity of Actinobacteria Associated with the Marine Ascidian Eudistoma toealensis. Mar. Biotechnol. 2015, 17, 377–385. [Google Scholar] [CrossRef]
- De Menezes, C.B.; Afonso, R.S.; de Souza, W.R.; Parma, M.; de Melo, I.S.; Zucchi, T.D.; Fantinatti-Garboggini, F. Gordonia didemni sp. nov. an actinomycete isolated from the marine ascidium Didemnum sp. Antonie van Leeuwenhoek 2016, 109, 297–303. [Google Scholar] [CrossRef]
- Franzetti, A.; Caredda, P.; Ruggeri, C.; La Colla, P.; Tamburini, E.; Papacchini, M.; Bestetti, G. Potential applications of surface active compounds by Gordonia sp. strain BS29 in soil remediation technologies. Chemosphere 2009, 75, 801–807. [Google Scholar] [CrossRef]
- Kim, S.H.; Yang, H.O.; Sohn, Y.C.; Kwon, H.C. Aeromicrobium halocynthiae sp. nov., a taurocholic acid-producing bacterium isolated from the marine ascidian Halocynthia roretzi. Int. J. Syst. Evol. Microbiol. 2010, 60 Pt 12, 2793–2798. [Google Scholar] [CrossRef] [PubMed]
- Kim, D.; Lee, J.S.; Kim, J.; Kang, S.J.; Yoon, J.H.; Kim, W.G.; Lee, C.H. Biosynthesis of bile acids in a variety of marine bacterial taxa. J. Microbiol. Biotechnol. 2007, 17, 403–407. [Google Scholar] [PubMed]
- Wyche, T.P.; Alvarenga, R.F.R.; Piotrowski, J.S.; Duster, M.N.; Warrack, S.R.; Cornilescu, G.; De Wolfe, T.J.; Hou, Y.; Braun, D.R.; Ellis, G.A.; et al. Chemical Genomics, Structure Elucidation, and in Vivo Studies of the Marine-Derived Anticlostridial Ecteinamycin. ACS Chem. Biol. 2017, 12, 2287–2295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wyche, T.P.; Standiford, M.; Hou, Y.; Braun, D.; Johnson, D.A.; Johnson, J.A.; Bugni, T.S. Activation of the nuclear factor E2-related factor 2 pathway by novel natural products halomadurones A-D and a synthetic analogue. Mar. Drugs 2013, 11, 5089–5099. [Google Scholar] [CrossRef] [Green Version]
- Buedenbender, L.; Carroll, A.; Ekins, M.; Kurtböke, D. Taxonomic and Metabolite Diversity of Actinomycetes Associated with Three Australian Ascidians. Diversity 2017, 9, 53. [Google Scholar] [CrossRef] [Green Version]
- Buedenbender, L.; Robertson, L.P.; Lucantoni, L.; Avery, V.M.; Kurtboke, D.I.; Carroll, A.R. HSQC-TOCSY Fingerprinting-Directed Discovery of Antiplasmodial Polyketides from the Marine Ascidian-Derived Streptomyces sp. (USC-16018). Mar. drugs 2018, 16, 189. [Google Scholar] [CrossRef] [Green Version]
- Subramani, R.; Aalbersberg, W. Culturable rare Actinomycetes: Diversity, isolation and marine natural product discovery. Appl. Microbiol. Biotechnol. 2013, 97, 9291–9321. [Google Scholar] [CrossRef]
- Harunari, E.; Hamada, M.; Shibata, C.; Tamura, T.; Komaki, H.; Imada, C.; Igarashi, Y. Streptomyces hyaluromycini sp. nov., isolated from a tunicate (Molgula manhattensis). J. Antibiot. 2016, 69, 159–163. [Google Scholar] [CrossRef]
- Pelaez, F. The historical delivery of antibiotics from microbial natural products--can history repeat? Biochem. Pharmcol. 2006, 71, 981–990. [Google Scholar] [CrossRef]
- Anderson, A.S.; Wellington, E.M. The taxonomy of Streptomyces and related genera. Int J. Syst. Evol. Microbiol. 2001, 51, 797–814. [Google Scholar] [CrossRef] [Green Version]
- Malmstrom, J.; Christophersen, C.; Frisvad, J.C. Secondary metabolites characteristic of Penicillium citrinum, Penicillium steckii and related species. Phytochemistry 2000, 54, 301–309. [Google Scholar] [CrossRef]
- Jang, W.S.; Kim, H.K.; Lee, K.Y.; Kim, S.A.; Han, Y.S.; Lee, I.H. Antifungal activity of synthetic peptide derived from halocidin, antimicrobial peptide from the tunicate, Halocynthia aurantium. FEBS Lett. 2006, 580, 1490–1496. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamazaki, H.; Nakayama, W.; Takahashi, O.; Kirikoshi, R.; Izumikawa, Y.; Iwasaki, K.; Toraiwa, K.; Ukai, K.; Rotinsulu, H.; Wewengkang, D.S.; et al. Verruculides A and B, two new protein tyrosine phosphatase 1B inhibitors from an Indonesian ascidian-derived Penicillium verruculosum. Bioorg. Med. Chem. Lett. 2015, 25, 3087–3090. [Google Scholar] [CrossRef] [PubMed]
- Sumilat, D.A.; Yamazaki, H.; Endo, K.; Rotinsulu, H.; Wewengkang, D.S.; Ukai, K.; Namikoshi, M. A new biphenyl ether derivative produced by Indonesian ascidian-derived Penicillium albobiverticillium. J. Nat. Med. 2017, 71, 776–779. [Google Scholar] [CrossRef]
- Chen, S.; Jiang, M.; Chen, B.; Salaenoi, J.; Niaz, S.I.; He, J.; Liu, L. Penicamide A, A Unique N,N′-Ketal Quinazolinone Alkaloid from Ascidian-Derived Fungus Penicillium sp. 4829. Mar. Drugs 2019, 17, 522. [Google Scholar] [CrossRef] [Green Version]
- Shaala, L.A.; Youssef, D.T. Identification and bioactivity of compounds from the fungus Penicillium sp. CYE-87 isolated from a marine tunicate. Mar. Drugs 2015, 13, 1698–1709. [Google Scholar] [CrossRef] [Green Version]
- Motohashi, K.; Hashimoto, J.; Inaba, S.; Khan, S.T.; Komaki, H.; Nagai, A.; Takagi, M.; Shin-ya, K. New sesquiterpenes, JBIR-27 and -28, isolated from a tunicate-derived fungus, Penicillium sp. SS080624SCf1. J. Antibiot. 2009, 62, 247–250. [Google Scholar] [CrossRef]
- Ivanets, E.V.; Yurchenko, A.N.; Smetanina, O.F.; Rasin, A.B.; Zhuravleva, O.I.; Pivkin, M.V.; Popov, R.S.; von Amsberg, G.; Afiyatullov, S.S.; Dyshlovoy, S.A. Asperindoles A(-)D and a p-Terphenyl Derivative from the Ascidian-Derived Fungus Aspergillus sp. KMM 4676. Mar. Drugs 2018, 16, 232. [Google Scholar] [CrossRef] [Green Version]
- Montenegro, T.G.; Rodrigues, F.A.; Jimenez, P.C.; Angelim, A.L.; Melo, V.M.; Rodrigues Filho, E.; de Oliveira Mda, C.; Costa-Lotufo, L.V. Cytotoxic activity of fungal strains isolated from the ascidian Eudistoma vannamei. Chem. Biodivers 2012, 9, 2203–2209. [Google Scholar] [CrossRef]
- Dewapriya, P.; Prasad, P.; Damodar, R.; Salim, A.A.; Capon, R.J. Talarolide A, a Cyclic Heptapeptide Hydroxamate from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. (CMB-TU011). Org. Lett. 2017, 19, 2046–2049. [Google Scholar] [CrossRef]
- Chen, S.; Shen, H.; Zhang, P.; Cheng, H.; Dai, X.; Liu, L. Anti-glioma trichobamide A with an unprecedented tetrahydro-5H-furo[2,3-b]pyrrol-5-one functionality from ascidian-derived fungus Trichobotrys effuse 4729. Chem. Commun. 2019, 55, 1438–1441. [Google Scholar] [CrossRef] [PubMed]
- Yarden, O. Fungal association with sessile marine invertebrates. Front. Microbiol. 2014, 5, 228. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Brandt, D.; Thakur, N.L.; Wiens, M.; Batel, R.; Schröder, H.C.; Müller, W.E.G. Molecular cross-talk between sponge host and associated microbes. Phytochem. Rev. 2012, 12, 369–390. [Google Scholar] [CrossRef]
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Dou, X.; Dong, B. Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts. Mar. Drugs 2019, 17, 670. https://doi.org/10.3390/md17120670
Dou X, Dong B. Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts. Marine Drugs. 2019; 17(12):670. https://doi.org/10.3390/md17120670
Chicago/Turabian StyleDou, Xiaoju, and Bo Dong. 2019. "Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts" Marine Drugs 17, no. 12: 670. https://doi.org/10.3390/md17120670