Abstract
In the new global economy, technological advancement, increasing population density, ageing and widely reported sanitary problems intensified by social underdevelopment have justified an increasing need for sustainable and effective measures to alleviate some of the most common burdens the society has suffered from, as broadly reported by the World Health Organization (WHO). The global health has increasingly become a central issue in promoting individual wellbeing, which directly affects collective progress. Over the past decade, pharmaceutical companies have massively invested in new technologies, aiming at discovering new chemicals and progressing knowledge in synthetic compounds and in high-throughput workflows. In plant science, high-throughput screening (HTS) strongly supports drug discovery by accelerating the screening of biologically diverse samples, which at its very basic stages involves the isolation of biota samples and the determination of the structure of the underlying bio-actives. The resulting automation chain brings about fast-paced effective production of medicinal molecules, excelling in performance conventional approaches. Nevertheless, HTS is one single example of how technology has positively contributed to drug discovery. Since the beginning of civilisation, medicinal plants have offered the fundamental means to humankind for fighting diseases. In the current literature, it has been reported that more than 200,000 plant derivatives, among which key natural products, are being used in therapies for treating severe health conditions such as congestive heart failure and cardiac arrhythmias. However, production yield and compounds toxicity are still among the fundamental barriers of compounds production and drug discovery. Gene editing is another fruitful example of biotechnology-driven production of compounds. A growing body of literature has reported on CRISPR-Cas 9 modifying gene expression, whose phenotype is fundamental in modulating the biosynthesis of bio-active compounds. Ultimately, artificial intelligence (AI) is arriving strongly, potentially to stay, and impacting the pharmaceutical sector. Several consortiums have been formed and companies founded, over the last few years, with the purpose of applying AI technology in molecular design, drug screening and genotype-phenotype analysis for predicting drug activity in genetically engineered species. However, we have constantly argued on the need for increasing efforts towards improving plant metabolites production, via biotechnological resources, mainly recombinant-DNA technology: first, because certain compounds are scarce in nature, and second, because new bio-actives could bring about genetically engineered plant cells. Hence, the aim of this chapter is to review recent progress in the production of plant bio-active compounds promoted by biotechnological advancement.
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References
Abbai R, Subramaniyam S, Mathiyalagan R, Yang DC (2017) Functional genomic approaches in plant research. In: Hakeem KR, Malik A, Vardar-Sukan F, Ozturk M (eds) Plant bioinformatics. Springer, Cham, pp 215–239
Anantharaman P, Vallinayagam K, Arumugam R et al (2009) Antibacterial activity of some selected seaweeds from Pudumadam Coastal regions. Global Journal of Pharmacology 3:50–52
Arya V, Thakur N, Kashyap CP (2012) Preliminary phytochemical analysis of the extracts of Psidium leaves. J Pharmacogn Phytochem 1:1–5
Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, Temml V, Wang L, Schwaiger S, Heiss EH, Rollinger JM, Schuster D, Breuss JM, Bochkov V, Mihovilovic MD, Kopp B, Bauer R, Dirsch VM, Stuppner H (2015) Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 33:1582–1614
Badenes ML, Martí AF, Ríos G, Rubio-Cabetas MJ (2016) Application of genomic technologies to the breeding of trees. Front Genet 7:198. https://doi.org/10.3389/fgene.2016.00198
Barrangou R, Doudna JA (2016) Applications of CRISPR technologies in research and beyond. Nat Biotechnol 34:933–941
Belhaj K, Chaparro-Garcia A, Kamoun S, Patron NJ, Nekrasov V (2015) Editing plant genomes with CRISPR/Cas9. Curr Opin Biotechnol 32:76–84
Bindseil KU, Jakupovic J, Wolf D, Lavayre J, Leboul J, van der Pyl D (2001) Pure compound libraries; a new perspective for natural product based drug discovery. Drug Discov Today 6:840–847
Chen L, Li W, Katin-Grazzini L, Ding J, Gu X, Li Y, Gu T, Wang R, Lin X, Deng Z, McAvoy RJ, Gmitter FG Jr, Deng Z, Zhao Y, Li Y (2018) A method for the production and expedient screening of CRISPR/Cas9-mediated non-transgenic mutant plants. Hort Res 5:13. https://doi.org/10.1038/s41438-018-0023-4
Cuperlovic-Culf M, Culf AS (2016) Applied metabolomics in drug discovery. Expert Opin Drug Discovery 11:759–770
Demunshi Y, Chugh A (2010) Role of traditional knowledge in marine bioprospecting. Biodivers Conserv 19:3015–3033
Dhanani T, Shah S, Gajbhiye NA, Kumar S (2017) Effect of extraction methods on yield, phytochemical constituents and antioxidant activity of Withania somnifera. Arab J Chem 10:S1193–S1199
Do QD, Angkawijaya AE, Tran-Nguyen PL, Huynh LH, Soetaredjo FE, Ismadji S, Ju YH (2014) Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica. J Food Drug Anal 22:296–302
Domínguez H, González Muñoz MJ (2017) Water extraction of bioactive compounds: from plants to drug development. Elsevier, UK
Dvorackova E, Snoblova M, Chromcova L, Hrdlicka P (2015) Effects of extraction methods on the phenolic compounds contents and antioxidant capacities of cinnamon extracts. Food Sci Biotechnol 24:1201–1207
Eggert US (2013) The why and how of phenotypic small-molecule screens. Nat Publ Gr 9:206–209
Eldridge GR, Vervoort HC, Lee CM, Cremin PA, Williams CT, Hart SM, Goering MG, O’Neil-Johnso M, Zeng L (2002) High-throughput method for the production and analysis of large natural product libraries for drug discovery. Anal Chem 74:3963–3971
Elfahmi, Suhandono S, Chahyadi A (2014) Optimization of genetic transformation of Artemisia annua L. using Agrobacterium for Artemisinin production. Pharmacogn Mag 10:S176–S180
Fleming N (2018) How artificial intelligence is changing drug discovery. Nature 2018:5577707
Galeon D, Houser K (2016) IBM’s watson AI recommends same treatment as doctors in 99% of cancer cases. https://futurism.com/ibms-watson-ai-recommends-same-treatment-as-doctors-in-99-of-cancer-cases/. Accessed 16 Sept 2018
Gascuel Q, Diretto G, Monforte AJ, Fortes AM, Granell A (2017) Use of natural diversity and biotechnology to increase the quality and nutritional content of tomato and grape. Front Plant Sci 8:652. https://doi.org/10.3389/fpls.2017.00652
Gibney E (2016) Google AI algorithm masters ancient game of go. Nature 529:445–446
GNS Healthcare (2017) GNS healthcare announces collaboration to power cancer drug development with REFSTM causal machine learning and simulation AI Platform, GNS HealthCare. http://www.gnshealthcare.com/news/gns-healthcare-announces-collaboration-to-power-cancer-drug-development/. Accessed 16 Jul 2018
Groneman AF, Posthumus MA, Tuinstra LGMT, Traag WA (1984) Identification and determination of metabolites in plant cell biotechnology by gas chromatography and gas chromatography/mass spectrometry: application to non-polar products of Chrysanthemum cinerariaefolium and Tagetes species. Anal Chim Acta 163:43–54
Guerrero MF, Puebla P, Carrón R, Martín ML, Arteaga L, Román LS (2002) Assessment of the antihypertensive and vasodilator effects of ethanolic extracts of some Colombian medicinal plants. J Ethnopharmacol 80(1):37–42
Handa SS (2008) An overview of extraction techniques for medicinal and aromatic plants. In: SS K, Longo G, Rakesh DD (eds) Extraction technologies for medicinal and aromatic plants. International Centre for Science and High Technology, Trieste, pp 21–25
Hartung F, Schiemann J (2014) Precise plant breeding using new genome editing techniques: opportunities, safety and regulation in the EU. Plant J 78:742–752
Harvey AL, Edrada-Ebel R, Quinn RJ (2015) The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 14:111–129
Hochrein L, Mitchell LA, Schulz K, Messerschmidt K, Mueller-Roeber B (2018) L-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast. Nat Commun 9:1931. https://doi.org/10.1038/s41467-017-02208-6
Hubbard AL, Wilson SM, Callan DE, Dapretto M (2009) Giving speech a hand: gesture modulates activity in auditory cortex during speech perception. Hum Brain Mapp 30:1028–1037
Huie CW (2002) A review of modern sample-preparation techniques for the extraction and analysis of medicinal plants. Anal Bioanal Chem 373:23–30
Hunt B, Vincent ACJ (2006) Scale and sustainability of marine bioprospecting for pharmaceuticals. AMBIO J Hum Environ 35(2):57–64
Hutson M (2017) Self-taught artificial intelligence beats doctors at predicting heart attacks. Science (Online). https://doi.org/10.1126/science.aal1058
Ishii T, Araki M (2017) A future scenario of the global regulatory landscape regarding genome-edited crops. GM Crops Food 8:44–56
Iwasaki Y, Sawada T, Hatayama K, Ohyagi A, Tsukuda Y, Namekawa K, Ito R, Saito K, Nakazawa H (2012) Separation technique for the determination of highly polar metabolites in biological samples. Metabolites 2:496–515
Japsen B (2016) Pfizer partners with IBM watson to advance cancer drug discovery. https://www.forbes.com/sites/brucejapsen/2016/12/01/pfizer-partners-with-ibm-watson -to-advance-cancer-drug-discovery/#1ab32abe1b1e. Accessed 16 Sept 2018
Kanchiswamy CN, Malnoy M, Velasco R, Kim JS, Viola R (2015) Non-GMO genetically edited crop plants. Trends Biotechnol 33:489–491
Kellenberger E, Hofmann A, Quinn RJ (2011) Similar interactions of natural products with biosynthetic enzymes and therapeutic targets could explain why nature produces such a large proportion of existing drugs. Nat Prod Rep 28:1483
Key S, Ma JKC, Drake PM (2008) Genetically modified plants and human health. J Royal Soc Med 101:290–298
Kopertekh L, Krebs E, Guzmann F (2018) Improvement of conditional Cre-lox system through application of the regulatory sequences from Cowpea mosaic virus. Plant Biotechnol Rep 12:127–137
Kosicki M, Tomberg K, Bradley A (2018) Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol 36:765–771
Kumar B, Prakash A, Ruhela RK, Medhi B (2014) Potential of metabolomics in preclinical and clinical drug development. Pharmacol Rep 66:956–963
Ledford H (2018) CRISPR gene editing produces unwanted DNA deletions. Nature (online). doi: d41586-018-05736-3
Lee N, Shin J, Park JH, Lee GM, Cho S, Cho BK (2016) Targeted gene deletion using DNA-free RNA-guided Cas9 nuclease accelerates adaptation of CHO cells to suspension culture. ACS Synth Biol 5:1211–1219
Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, Lv J, **e X, Chen Y, Li Y, Sun Y (2015) CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6:363–372
Macarron R, Banks MN, Bojanic D, Burns DJ, Cirovic DA, Garyantes T, Green DV, Hertzberg RP, Janzen WP, Paslay JW, Schopfer U (2011) Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov 10:188–195
Mears AJ, Schock SC, Hadwen J, Putos S, Dyment D, Boycott KM, MacKenzie A (2017) Mining the transcriptome for rare disease therapies: a comparison of the efficiencies of two data mining approaches and a targeted cell-based drug screen. Genomic Med 2:14. https://doi.org/10.1038/s41525-017-0018-3
Ng SB, Kanagasundaram Y, Fan H, Arumugam P, Eisenhaber B, Eisenhaber F (2018) The 160K natural organism library, a unique resource for natural products research. Nat Biotechnol 36:570–573
Od A, Io E (2016) Impact and challenges of marine medicine to man and its environment. Poultry, Fish Wildl Sci 4:1–11
Olson P (2017) This AI just beat human doctors on a clinical exam. https://www.forbes.com/sites/parmyolson/2018/06/28/ai-doctors-exam-babylon-health/#1c5b37ac12c0. Accessed 16 Sept 2018
Osakabe Y, Sugano SS, Osakabe K (2016) Genome engineering of woody plants: past, present and future. J Wood Sci 62:217–225
Pereira GC (2017) Genomics and artificial intelligence working together in drug discovery and repositioning: the advent of adaptive pharmacogenomics in glioblastoma and chronic arterial inflammation therapies. In: Malik S (ed) Biotechnology and production of anticancer compounds. Springer, Cham, pp 253–281
Pereira RC, Costa-Lotufo LV (2012) Bioprospecting for bioactives from seaweeds: potential, obstacles and alternatives. Rev Bras Farmacogn 22:894–905
Press G (2016) A very short history of artificial intelligence (AI). Forbes 115–133
Rai A, Saito K, Yamazaki M (2017) Integrated omics analysis of specialized metabolism in medicinal plants. Plant J 90:764–787
Rawat P, Singh PK, Kumar V (2016) Anti-hypertensive medicinal plants and their mode of action. J Herb Med 6:107–118
Rinehart KL, Holt TG, Fregeau NL, Stroh JG, Keifer PA, Sun F, Li LH, Martin DG (1990) Ecteinascidins 729, 743, 745, 759A, 759B, and 770: potent antitumor agents from the Caribbean tunicate Ecteinascidia turbinata. J Org Chem 55(15):4512–4515
Sasidharan S, Chen Y, Saravanan D et al (2011) Extraction, isolation and characterization of bioactive compounds from plants’ extracts. Afr J Tradit Compl Altern Med 8:1–10
Schenone M, Dančík V, Wagner BK, Clemons PA (2013) Target identification and mechanism of action in chemical biology and drug discovery. Nat Chem Biol 9:232–240
Scudellari M (2018) Q & Amp; A: AI could ‘Redesign’ the drug development process – IEEE spectrum. https://sola.ai/a-i-and-robotics/q-a-ai-could-redesign-the-drug-development-process-ieee-NWE0OTN. Accessed 16 Sept 2018
Serrano M, Kombrink E, Meesters C (2015) Considerations for designing chemical screening strategies in plant biology. Front Plant Sci 6:131. https://doi.org/10.3389/fpls.2015.00131
Smit AJ (2004) Medicinal and pharmaceutical uses of seaweed natural products: a review. J Appl Phycol 16:245–262
Sobhani Z, Reza Nami S, Ahmad Emami S, Sahebkar A, Javadi B (2017) Medicinal plants targeting cardiovascular diseases in view of Avicenna. Curr Pharm Des 23:2428–2443
Song AJ, Palmiter RD (2018) Detecting and avoiding problems when using the Cre-lox system. Trends Genet 34:333–340
Soquetta MB, de Terra LM, Bastos CP (2018) Green technologies for the extraction of bioactive compounds in fruits and vegetables. CyTA J Food 16:400–412
Spigno G, Tramelli L, De Faveri DM (2007) Effects of extraction time, temperature and solvent on concentration and antioxidant activity of grape marc phenolics. J Food Eng 81(1):200–208
Strickland E (2017) AI predicts heart attacks and strokes more accurately than standard doctor’s method. https://spectrum.ieee.org/the-human-os/biomedical/diagnostics/ai-predicts-heart-attacks-more-accurately-than-standard-doctor-method. Accessed 16 Sept 2018
Subchefia para Assuntos Jurídicos (2005) Presidência da República Casa Civil: LEI No 11.105, DE 24 DE MARÇO DE 2005. http://www.planalto.gov.br/ccivil_03/_Ato2004-2006/2005/Lei/L11105.htm#art42
Thomas TRA, Kavlekar DP, Loka Bharathi PA (2010) Marine drugs from sponge-microbe association-a review. Mar Drugs 8:1417–1468
Tittensor DP, Mora C, Jetz W, Lotze HK, Ricard D, Vanden Berghe E, Worm B (2010) Global patterns and predictors of marine biodiversity across taxa. Nature 466(7310):1098–1101
Trusheva B, Trunkova D, Bankova V (2007) Different extraction methods of biologically active components from propolis: a preliminary study. Chem Cent J 1:13. https://doi.org/10.1186/1752-153X-1-13
Vo TS, Kim SK (2010) Potential anti-HIV agents from marine resources: an overview. Mar Drugs 8:2871–2892
Wagenaar MM (2008) Pre-fractionated microbial samples – the second generation natural products library at Wyeth. Molecules 13:1406–1426
Waksmundzka-Hajnos M, Sherma J (2010) High performance liquid chromatography in phytochemical analysis. CRC Press, Boca Raton
Waters AL, Hill RT, Place AR, Hamann MT (2010) The expanding role of marine microbes in pharmaceutical development. Curr Opin Biotechnol 21:780–786
Wetzel S, Bon RS, Kumar K, Waldmann H (2011) Biology-oriented synthesis. Angew Chem Int Ed 50:10800–10826
Wink M (2003) Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry 64:3–19
Wishart DS (2016) Emerging applications of metabolomics in drug discovery and precision medicine. Nat Rev Drug Discov 15:473–484
**n Y, Guo T, Mu Y, Kong J (2018) Coupling the recombineering to Cre-lox system enables simplified large-scale genome deletion in Lactobacillus casei. Microb Cell Factories 17:21. https://doi.org/10.1186/s12934-018-0872-4
Xu J, Hou H, Hu J, Liu B (2018) Optimized microwave extraction, characterization and antioxidant capacity of biological polysaccharides from Eucommia ulmoides oliver leaf. Sci Rep 8:6561. https://doi.org/10.1038/s41598-018-24957-0
Yan L (2018) Chinese ai beats doctors in diagnosing brain tumors. https://www.popularmechanics.com/technology/robots/a22148464/chinese-ai-diagnosed-brain-tumors-more-accurately-physicians/. Accessed 16 Sept 2018
Yang F, Liu C, Chen D, Tu M, **e H, Sun H, Ge X, Tang L, Li J, Zheng J, Song Z (2017) CRISPR/Cas9-loxP-mediated gene editing as a novel site-specific genetic manipulation tool. Mol Ther Nucleic Acids 7:378–386
Ymele-Leki P, Cao S, Sharp J, Lambert KG, McAdam AJ, Husson RN, Tamayo G, Clardy J, Watnick PI (2012) A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity. PLoS One 7:e31307. https://doi.org/10.1371/journal.pone.0031307
Zhang QW, Lin LG, Ye WC (2018a) Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med 13:20. https://doi.org/10.1186/s13020-018-0177-x
Zhang Y, Wu X, Duan T, Xu J, Dong F, Liu X, Li X, Du P, Zheng Y (2018b) Ultra high performance liquid chromatography with tandem mass spectrometry method for determining dinotefuran and its main metabolites in samples of plants, animal-derived foods, soil, and water. J Sep Sci. https://doi.org/10.1002/jssc.201701551
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The author is grateful for the invitation to contribute with this chapter. Equally, the author is grateful to all those who directly and indirectly contributed with the success of the research undertaken over nearly 19 years spent in academia, e.g. Institut Carnot (ICM – France), MCINN (Spain), the BHF (the UK), CnPq (Brazil), Capes (Brazil), and others.
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Pereira, G.C. (2019). Application of Biotechnology in Producing Plant Bio-active Compounds. In: Akhtar, M., Swamy, M. (eds) Natural Bio-active Compounds. Springer, Singapore. https://doi.org/10.1007/978-981-13-7438-8_3
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