Marine Biotechnology and Its Applications in Drug Discovery

The Ocean is the largest biome on our planet Earth with the greatest extremities of temperature and climatic conditions. High ionic concentrations, high pressures and both low and high temperatures define this particular environment. Marine (Blue) biotechnology is the use of biological resources from the ocean for industrial, medical or environmental purposes. Marine Biotechnology can also be defined as a cutting-edge era of science and technology that majorly focuses on marine resources to support living creatures. Due to the ecologically and environmentally diverse sea environment, the planet’s most chemically varied ecosystem, marine biotechnology, has been recently known to produce an increasing number of key medicinal goods, industrial and environmental tools and applications for varied research analysis. This book delves deeper into the prospective use of marine biotechnology for drug discovery, including the development of enzymes, antibiotics and biopolymers, substances derived from various marine sources. In fact, the potential for natural products offered by marine microbial biodiversity appears to be endless and vast expanding as new methods of measurement are being developed. One of the prerequisite factors for successful innovation in exploiting the enormous diversity of marine life is high-quality research in the field of marine biotechnology.

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References

• Aguilar A, Magnien E, Thomas D (2013) Thirty years of European biotechnology programmes: from biomolecular engineering to the bioeconomy. New Biotechnol 30(5):410–425. https://doi.org/10.1016/j.nbt.2012.11.014ArticleCASGoogle Scholar
• Aminin DL, Menchinskaya ES, Pisliagin EA, Silchenko AS, Avilov SA, Kalinin VI (2015) Anticancer activity of sea cucumber triterpene glycosides. Mar Drugs 13(3):1202–1223. https://doi.org/10.3390/md13031202ArticleCASPubMedPubMed CentralGoogle Scholar
• Aminov RI (2010) A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol 1:134. https://doi.org/10.3389/fmicb.2010.00134ArticlePubMedPubMed CentralGoogle Scholar
• Andersen KH, Berge T, Gonçalves RJ, Hartvig M, Heuschele J, Hylander S, Jacobsen NS, Lindemann C, Martens EA, Neuheimer AB, Olsson K, Palacz A, Prowe AEF, Sainmont J, Traving SJ, Visser AW, Wadhwa N, Kiørboe T (2016) Characteristic sizes of life in the oceans, from bacteria to whales. Annu Rev Mar Sci 8:217–241. https://doi.org/10.1146/annurev-marine-122414-034144ArticleCASGoogle Scholar
• Ang KK, Holmes MJ, Higa T, Hamann MT, Kara UA (2000) In vivo antimalarial activity of the beta-carboline alkaloid manzamine A. Antimicrob Agents Chemother 44(6):1645–1649. https://pubmed.ncbi.nlm.nih.gov/10817722/ArticleCASPubMedPubMed CentralGoogle Scholar
• Auala T, Zavale BG, Mbakwem AÇ, Mocumbi AO (2022) Acute rheumatic fever and rheumatic heart disease: highlighting the role of group a streptococcus in the global burden of cardiovascular disease. Pathogens 11(5):496. https://doi.org/10.3390/pathogens11050496ArticleCASPubMedPubMed CentralGoogle Scholar
• Barcelos MCS, Lupki FB, Campolina GA, Nelson DL, Molina G (2018) The colors of biotechnology: general overview and developments of white, green and blue areas. FEMS Microbiol Lett 365(21). https://doi.org/10.1093/femsle/fny239
• Bays HE, Tighe AP, Sadovsky R, Davidson MH (2008) Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 6(3):391–409. https://doi.org/10.1586/14779072.6.3.391ArticleCASPubMedGoogle Scholar
• Bazinet RP, Chu MWA (2014) Omega-6 polyunsaturated fatty acids: is a broad cholesterol-lowering health claim appropriate? Can Med Assoc J 186(6):434–439. https://doi.org/10.1503/cmaj.130253ArticleGoogle Scholar
• Bergmann W, Stempien MF (1957) Contributions to the study of marine products. XLIII. The nucleosides of sponges. V. the synthesis of spongosine1. J Org Chem 22(12):1575–1577. https://doi.org/10.1021/jo01363a009ArticleCASGoogle Scholar
• Bhatnagar I, Kim S-K (2010) Immense essence of excellence: marine microbial bioactive compounds. Mar Drugs 8(10):2673–2701. https://doi.org/10.3390/md8102673ArticleCASPubMedPubMed CentralGoogle Scholar
• Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR (2004) Marine natural products. Nat Prod Rep 21(1):1–49. https://doi.org/10.1039/B305250HArticleCASPubMedGoogle Scholar
• Boeuf G (2011) Marine biodiversity characteristics. C R Biol 334(5):435–440. https://doi.org/10.1016/j.crvi.2011.02.009ArticlePubMedGoogle Scholar
• Brodeur RD, Auth TD, Phillips AJ (2019) Major shifts in pelagic micronekton and macrozooplankton community structure in an upwelling ecosystem related to an unprecedented marine heatwave. Front Mar Sci 6:212 ArticleGoogle Scholar
• Carte BK (1996) Biomedical potential of marine natural products. Bioscience 46(4):271–286. https://www.jstor.org/stable/1312834ArticleGoogle Scholar
• Chhetry M, Jialal I (2022) Lipid lowering drug therapy. In: StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK541128/
• D’Incalci M, Galmarini CM (2010) A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther 9(8):2157–2163. https://doi.org/10.1158/1535-7163.MCT-10-0263ArticleCASPubMedGoogle Scholar
• Dipper F (2022) Chapter 4 - Open water lifestyles: marine plankton. In: Dipper F (ed) Elements of marine ecology, 5th edn. Butterworth-Heinemann, pp 193–228. https://doi.org/10.1016/B978-0-08-102826-1.00005-3ChapterGoogle Scholar
• Donia M, Hamann MT (2003) Marine natural products and their potential applications as anti-infective agents. Lancet Infect Dis 3(6):338–348. https://doi.org/10.1016/S1473-3099(03)00655-8ArticleCASPubMedPubMed CentralGoogle Scholar
• Faircloth G, del Carmen Cuevas Marchante M (2006) Kahalalide F and ES285: potent anticancer agents from marine molluscs. In: Cimino G, Gavagnin M (eds) Molluscs: from chemo-ecological study to biotechnological application. Springer, pp 363–379. https://doi.org/10.1007/978-3-540-30880-5_16ChapterGoogle Scholar
• Fattorusso E, Taglialatela-Scafati O (2009) Marine antimalarials. Mar Drugs 7(2):130–152. https://doi.org/10.3390/md7020130ArticleCASPubMedPubMed CentralGoogle Scholar
• Gaisser S, Nusser M (2010) The role of biotechnology in pharmaceutical drug design. Zeitschrift Fur Evidenz, Fortbildung Und Qualitat Im Gesundheitswesen 104(10):732–737. https://doi.org/10.1016/j.zefq.2010.05.001ArticlePubMedGoogle Scholar
• Gayon J (2016) From Mendel to epigenetics: history of genetics. C R Biol 339:225. https://doi.org/10.1016/j.crvi.2016.05.009ArticlePubMedGoogle Scholar
• Ghosh S, Sarkar T, Pati S, Kari ZA, Edinur HA, Chakraborty R (2022) Novel bioactive compounds from marine sources as a tool for functional food development. Front Mar Sci 9. https://doi.org/10.3389/fmars.2022.832957
• Gupta V, Sengupta M, Prakash J, Tripathy BC (2016) An introduction to biotechnology. Basic Appl Aspects Biotechnol 1–21. https://doi.org/10.1007/978-981-10-0875-7_1
• Heiferman MJ, Salabat MR, Ujiki MB, Strouch MJ, Cheon EC, Silverman RB, Bentrem DJ (2010) Sansalvamide induces pancreatic cancer growth arrest through changes in the cell cycle. Anticancer Res 30(1):73–78 CASPubMedGoogle Scholar
• Hughes J, Rees S, Kalindjian S, Philpott K (2011) Principles of early drug discovery. Br J Pharmacol 162(6):1239–1249. https://doi.org/10.1111/j.1476-5381.2010.01127.xArticleCASPubMedPubMed CentralGoogle Scholar
• Irigoien X, Huisman J, Harris RP (2004) Global biodiversity patterns of marine phytoplankton and zooplankton. Nature 429(6994):863–867. https://doi.org/10.1038/nature02593ArticleCASPubMedGoogle Scholar
• Ismail AH, Adnan AAM (2016) Zooplankton composition and abundance as indicators of eutrophication in two small man-made lakes. Trop Life Sci Res 27(Supp 1):31–38. https://doi.org/10.21315/tlsr2016.27.3.5ArticlePubMedPubMed CentralGoogle Scholar
• Jha RK, Zi-Rong X (2004) Biomedical compounds from marine organisms. Mar Drugs 2(3):123–146. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783866/ArticleCASPubMed CentralGoogle Scholar
• Jiao W, Zhang F, Zhao X, Hu J, Suh J-W (2013) A novel alkaloid from marine-derived actinomycete streptomyces xinghaiensis with broad-spectrum antibacterial and cytotoxic activities. PLoS One 8(10):e75994. https://doi.org/10.1371/journal.pone.0075994ArticleCASPubMedPubMed CentralGoogle Scholar
• Jung HA, Islam MN, Lee CM, Oh SH, Lee S, Jung JH, Choi JS (2013) Kinetics and molecular docking studies of an anti-diabetic complication inhibitor fucosterol from edible brown algae Eisenia bicyclis and Ecklonia stolonifera. Chem Biol Interact 206(1):55–62. https://doi.org/10.1016/j.cbi.2013.08.013ArticleCASPubMedGoogle Scholar
• Kafarski P (2012) Rainbow code of biotechnology. Chemik 66(8):811–816. https://www.researchgate.net/publication/287253802_Rainbow_code_of_biotechnologyGoogle Scholar
• Kandasamy K, Nabeel MA, Manivannan S (2008) Bioprospecting of marine organisms for novel bioactive compounds. J Sci Trans Environ Technol 1:107–120. https://doi.org/10.20894/STET.116.001.003.001ArticleGoogle Scholar
• Kankal NC, Warudkar S (2012) Biodiversity of phytoplankton, zooplankton and zoobenthos in east coast, bay of Bengal near Nellore, Andhra Pradesh (INDIA) 1, 14 Google Scholar
• Kim S-K, Bhatnagar I, Kang K-H (2012) Development of marine probiotics: prospects and approach. Adv Food Nutr Res 65:353–362. https://doi.org/10.1016/B978-0-12-416003-3.00023-8ArticleGoogle Scholar
• Kroeker KJ, Micheli F, Gambi MC, Martz TR (2011) Divergent ecosystem responses within a benthic marine community to ocean acidification. Proc Natl Acad Sci U S A 108(35):14515–14520. https://doi.org/10.1073/pnas.1107789108ArticlePubMedPubMed CentralGoogle Scholar
• Kuczynska P, Jemiola-Rzeminska M, Strzalka K (2015) Photosynthetic pigments in diatoms. Mar Drugs 13(9):5847–5881. https://doi.org/10.3390/md13095847ArticleCASPubMedPubMed CentralGoogle Scholar
• Kumar R, Salwe KJ, Kumarappan M (2017) Evaluation of antioxidant, hypolipidemic, and antiatherogenic property of lycopene and astaxanthin in atherosclerosis-induced rats. Pharm Res 9(2):161–167. https://doi.org/10.4103/0974-8490.204654ArticleGoogle Scholar
• Lauritano C, Ianora A (2016) Marine organisms with anti-diabetes properties. Mar Drugs 14(12):220. https://doi.org/10.3390/md14120220ArticleCASPubMedPubMed CentralGoogle Scholar
• Lee S-H, Jeon Y-J (2013) Anti-diabetic effects of brown algae derived phlorotannins, marine polyphenols through diverse mechanisms. Fitoterapia 86:129–136. https://doi.org/10.1016/j.fitote.2013.02.013ArticleCASPubMedGoogle Scholar
• Li Y-X, Himaya SWA, Kim S-K (2013) Triterpenoids of marine origin as anti-cancer agents. Molecules (Basel, Switzerland) 18:7886–7909. https://doi.org/10.3390/molecules18077886ArticleCASPubMedGoogle Scholar
• Liang B, Cai X-Y, Gu N (2021) Marine natural products and coronary artery disease. Front Cardiovascular Med 8:739932. https://doi.org/10.3389/fcvm.2021.739932ArticleCASGoogle Scholar
• Lindequist U (2016) Marine-derived pharmaceuticals – challenges and opportunities. Biomol Ther 24(6):561–571. https://doi.org/10.4062/biomolther.2016.181ArticleCASGoogle Scholar
• Madhusudan S, Protheroe A, Propper D, Han C, Corrie P, Earl H, Hancock B, Vasey P, Turner A, Balkwill F, Hoare S, Harris AL (2003) A multicentre phase II trial of bryostatin-1 in patients with advanced renal cancer. Br J Cancer 89(8):1418–1422. https://doi.org/10.1038/sj.bjc.6601321ArticleCASPubMedPubMed CentralGoogle Scholar
• Malve H (2016) Exploring the ocean for new drug developments: marine pharmacology. J Pharm Bioallied Sci 8(2):83–91. https://doi.org/10.4103/0975-7406.171700ArticleCASPubMedPubMed CentralGoogle Scholar
• Manson JE, Cook NR, Lee I-M, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE (2019) Marine n−3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med 380(1):23–32. https://doi.org/10.1056/NEJMoa1811403ArticleCASPubMedGoogle Scholar
• Mayer AMS, Rodríguez AD, Taglialatela-Scafati O, Fusetani N (2013) Marine pharmacology in 2009–2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action. Mar Drugs 11(7):2510–2573. https://doi.org/10.3390/md11072510ArticleCASPubMedPubMed CentralGoogle Scholar
• Méresse S, Fodil M, Fleury F, Chénais B (2020) Fucoxanthin, a marine-derived carotenoid from brown seaweeds and microalgae: a promising bioactive compound for cancer therapy. Int J Mol Sci 21(23):9273. https://doi.org/10.3390/ijms21239273ArticleCASPubMedPubMed CentralGoogle Scholar
• Moon HE, Islam MN, Ahn BR, Chowdhury SS, Sohn HS, Jung HA, Choi JS (2011) Protein tyrosine phosphatase 1b and α-glucosidase inhibitory phlorotannins from edible brown algae, Ecklonia stolonifera and Eisenia bicyclis. Biosci Biotechnol Biochem 75(8):1472–1480. https://doi.org/10.1271/bbb.110137ArticleCASPubMedGoogle Scholar
• Mukhtar Y, Yunusa U, Galalain AM (2020) A modern overview on diabetes mellitus: a chronic endocrine disorder. Eur J Biol 5:1–14. https://doi.org/10.47672/ejb.409ArticleGoogle Scholar
• Nakao Y, Fusetani N (2010) 2.10 - marine invertebrates: sponges. In: Liu H-WB, Mander L (eds) Comprehensive natural products II. Elsevier, pp 327–362. https://doi.org/10.1016/B978-008045382-8.00043-5ChapterGoogle Scholar
• Olgunoglu İ (2017) Review on Omega-3 (n-3) fatty acids in fish and seafood. J Biol Agric Healthc 7:37–45 Google Scholar
• Ombelet W, Van Robays J (2015) Artificial insemination history: hurdles and milestones. Facts Views Vis ObGyn 7(2):137–143 CASPubMedPubMed CentralGoogle Scholar
• Ooi L-G, Liong M-T (2010) Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings. Int J Mol Sci 11(6):2499–2522. https://doi.org/10.3390/ijms11062499ArticleCASPubMedPubMed CentralGoogle Scholar
• Paudel P, Seong SH, Park HJ, Jung HA, Choi JS (2019) Anti-diabetic activity of 2,3,6-tribromo-4,5-dihydroxybenzyl derivatives from Symphyocladia latiuscula through PTP1B downregulation and α-glucosidase inhibition. Mar Drugs 17(3):166. https://doi.org/10.3390/md17030166ArticleCASPubMedPubMed CentralGoogle Scholar
• Pereira DM, Valentão P, Andrade PB (2014) Marine natural pigments: chemistry, distribution and analysis. Dyes Pigments 111:124–134. https://doi.org/10.1016/j.dyepig.2014.06.011ArticleCASGoogle Scholar
• Pouyan N (2019) Pasteur, A chemistry graduate who revoulotionized the medicine 148–151. https://doi.org/10.5923/j.microbiology.20140403.04
• Qiu Y, Jiang H, Fu L, Ci F, Mao X (2021) Porphyran and oligo-porphyran originating from red algae Porphyra: preparation, biological activities, and potential applications. Food Chem 349:129209. https://doi.org/10.1016/j.foodchem.2021.129209ArticleCASPubMedGoogle Scholar
• Rastogi A, Imadi S, Gul A (2016) Marine biotechnology: focus on anticancer drugs. In: Applied molecular biotechnology: the next generation of genetic engineering, pp 555–568. https://doi.org/10.1201/b19543-28
• Roehr M (2000) History of biotechnology in Austria. Adv Biochem Eng Biotechnol 69:125–149. https://doi.org/10.1007/3-540-44964-7_5ArticleCASPubMedGoogle Scholar
• Rotter A, Barbier M, Bertoni F, Bones AM, Cancela ML, Carlsson J, Carvalho MF, Cegłowska M, Chirivella-Martorell J, Conk Dalay M, Cueto M, Dailianis T, Deniz I, Díaz-Marrero AR, Drakulovic D, Dubnika A, Edwards C, Einarsson H, Erdoǧan A, Vasquez MI (2021) The essentials of marine biotechnology. Front Mar Science 8. https://doi.org/10.3389/fmars.2021.629629
• Sankarapandian V, Venmathi Maran BA, Rajendran RL, Jogalekar MP, Gurunagarajan S, Krishnamoorthy R, Gangadaran P, Ahn B-C (2022) An update on the effectiveness of probiotics in the prevention and treatment of cancer. Life 12(1):59. https://doi.org/10.3390/life12010059ArticleCASPubMedPubMed CentralGoogle Scholar
• Santana-Casiano JM, González-Dávila M, González AG, Millero FJ (2010) Fe(III) reduction in the presence of catechol in seawater. Aquat Geochem 16(3):467–482. https://doi.org/10.1007/s10498-009-9088-xArticleCASGoogle Scholar
• Schindler S (2008) Model, theory, and evidence in the discovery of the DNA structure. Br J Philos Sci 59(4):619–658. https://doi.org/10.1093/bjps/axn030ArticleGoogle Scholar
• Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71(1):7–33. https://doi.org/10.3322/caac.21654ArticlePubMedGoogle Scholar
• Sivamaruthi BS, Bharathi M, Kesika P, Suganthy N, Chaiyasut C (2021) The administration of probiotics against hypercholesterolemia: a systematic review. Appl Sci 11(15):6913. https://doi.org/10.3390/app11156913ArticleCASGoogle Scholar
• Smith K (2012) Louis Pasteur, the father of immunology? Front Immunol 3. https://doi.org/10.3389/fimmu.2012.00068
• Stryjewska A, Kiepura K, Librowski T, Lochyński S (2013) Biotechnology and genetic engineering in the new drug development. Part I. DNA technology and recombinant proteins. Pharmacol Rep 65(5):1075–1085. https://doi.org/10.1016/s1734-1140(13)71466-xArticleCASPubMedGoogle Scholar
• Tait RV (1972) Marine plankton. In: Tait RV (ed) Elements of marine ecology: an introductory course. Springer, pp 18–33. https://doi.org/10.1007/978-1-4613-8297-3_2ChapterGoogle Scholar
• Tan S, Tatsumura Y (2015) Alexander Fleming (1881–1955): discoverer of penicillin. Singap Med J 56(07):366–367. https://doi.org/10.11622/smedj.2015105ArticleGoogle Scholar
• Tong Y, Zhang X, Tian F, Yi Y, Xu Q, Li L, Tong L, Lin L, Ding J (2005) Philinopside A, a novel marine-derived compound possessing dual anti-angiogenic and anti-tumor effects. Int J Cancer 114(6):843–853. https://doi.org/10.1002/ijc.20804ArticleCASPubMedGoogle Scholar
• Trombetta T, Vidussi F, Roques C, Scotti M, Mostajir B (2020) Marine microbial food web networks during phytoplankton bloom and non-bloom periods: warming favors smaller organism interactions and intensifies trophic cascade. Front Microbiol 11. https://doi.org/10.3389/fmicb.2020.502336
• Turner T, Jackson WH, Pettit GR, Wells A, Kraft AS (1998) Treatment of human prostate cancer cells with dolastatin 10, a peptide isolated from a marine shell-less mollusc. Prostate 34(3):175–181. https://doi.org/10.1002/(SICI)1097-0045(19980215)34:33.0.CO;2-HArticleCASPubMedGoogle Scholar
• Verma AS, Agrahari S, Rastogi S, Singh A (2011) Biotechnology in the realm of history. J Pharmacy Bioallied Sci 3(3):321–323. https://doi.org/10.4103/0975-7406.84430ArticleCASGoogle Scholar
• Wright AE, Collins JE, Roberts B, Roberts JC, Winder PL, Reed JK, Diaz MC, Pomponi SA, Chakrabarti D (2021) Antiplasmodial compounds from deep-water marine invertebrates. Mar Drugs 19(4):179. https://doi.org/10.3390/md19040179ArticleCASPubMedPubMed CentralGoogle Scholar
• Xu Y, Zhu W, Wang T, Jin L, Liu T, Li X, Guan Z, Jiang Z, Meng X, Wang J, Guo Y (2019) Low molecule weight fucoidan mitigates atherosclerosis in ApoE (−/−) mouse model through activating multiple signal pathway. Carbohydr Polym 206:110–120. https://doi.org/10.1016/j.carbpol.2018.10.097ArticleCASPubMedGoogle Scholar
• Yang H-W, Fernando KHN, Oh J-Y, Li X, Jeon Y-J, Ryu B (2019) Anti-obesity and anti-diabetic effects of Ishige okamurae. Mar Drugs 17(4):202. https://doi.org/10.3390/md17040202ArticleCASPubMedPubMed CentralGoogle Scholar
• Zhang C, Kim S-K (2010) Research and application of marine microbial enzymes: status and prospects. Mar Drugs 8(6):1920–1934. https://doi.org/10.3390/md8061920ArticleCASPubMedPubMed CentralGoogle Scholar
• Zhang Y, Zhang J, Liang Y, Li H, Li G, Chen X, Liu J (2017) Carbon sequestration processes and mechanisms in coastal mariculture environments in China. Sci China Earth Sci 60(12):2097–2107 ArticleCASGoogle Scholar
• Zhang W, Tang X, Yang Y, Zhang X, Zhang X (2020) Elevated pCO2 level affects the extracellular polymer metabolism of Phaeodactylum tricornutum. Front Microbiol 11. https://doi.org/10.3389/fmicb.2020.00339
• Zhao J, Cao Q, Xing M, Xiao H, Cheng Z, Song S, Ji A (2020) Advances in the study of marine products with lipid-lowering properties. Mar Drugs 18(8):390. https://doi.org/10.3390/md18080390ArticleCASPubMedPubMed CentralGoogle Scholar

Acknowledgement

Thanks to the support provided by project no. LPA2007, MABIK, Korea to BAVM.