Chemical, physical and biotechnological approaches to the production of the potent antioxidant hydroxytyrosol

  • James Britton
  • Reeta Davis
  • Kevin E. O’ConnorEmail author


Hydroxytyrosol (HT) is a polyphenol of interooest to the food, feed, supplements and pharmaceutical sectors. It is one of the strongest known natural antioxidants and has been shown to confer other benefits such as anti-inflammatory and anti-carcinogenic properties, and it has the potential to act as a cardio- and neuroprotectant. It is known to be one of the compounds responsible for the health benefits of the Mediterranean diet. In nature, HT is found in the olive plant (Olea europaea) as part of the secoiridoid compound oleuropein, in its leaves, fruit, oil and oil production waste products. HT can be extracted from these olive sources, but it can also be produced by chemical synthesis or through the use of microorganisms. This review looks at the production of HT using plant extraction, chemical synthesis and biotechnological approaches.


Hydroxytyrosol Biocatalysis Olives Chemical synthesis Synthetic biology Tyrosinase 


Compliance with ethical standard

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Achak M, Hafidi A, Ouazzani N, Sayadi S, Mandi L (2009) Low cost biosorbent “banana peel” for the removal of phenolic compounds from olive mill wastewater: kinetic and equilibrium studies. J Hazard Mater 166:117–125. CrossRefGoogle Scholar
  2. Achmon Y, Fishman A (2014) The antioxidant hydroxytyrosol: biotechnological production challenges and opportunities. Appl Microbiol Biotechnol 99:1119–1130. CrossRefGoogle Scholar
  3. Agalias A, Magiatis P, Skaltsounis A-L, Mikros E, Tsarbopoulos A, Gikas E, Spanos I, Manios T (2007) A new process for the management of olive oil mill waste water and recovery of natural antioxidants. J Agric Food Chem 55:2671–2676. CrossRefGoogle Scholar
  4. Aissa I, Kharrat N, Aloui F, Sellami M, Bouaziz M, Gargouri Y (2017) Valorization of antioxidants extracted from olive mill wastewater. Biotechnol Appl Biochem 64:579–589. CrossRefGoogle Scholar
  5. Alburquerque J, Gonzálvez J, García D, Cegarra J (2004) Agrochemical characterisation of “alperujo”, a solid by-product of the two-phase centrifugation method for olive oil extraction. Bioresour Technol 91:195–200. CrossRefGoogle Scholar
  6. Allouche N, Sayadi S (2005) Synthesis of hydroxytyrosol, 2-hydroxyphenylacetic acid, and 3-hydroxyphenylacetic acid by differential conversion of tyrosol isomers using Serratia marcescens strain. J Agric Food Chem 53:6525–6530. CrossRefGoogle Scholar
  7. Allouche N, Damak M, Ellouz R, Sayadi S (2004a) Use of whole cells of Pseudomonas aeruginosa for synthesis of the antioxidant hydroxytyrosol via conversion of tyrosol. Appl Environ Microbiol 70:2105–2109. CrossRefGoogle Scholar
  8. Allouche N, Ines F, Sayadi S (2004b) Toward a high yield recovery of antioxidants and purified hydroxytyrosol from olive mill wastewaters. J Agric Food Chem 52:267–273. CrossRefGoogle Scholar
  9. Amiot M-J, Fleuriet A, Macheix J-J (1986) Importance and evolution of phenolic compounds in olives during growth and maturation. J Agric Food Chem 34:823–826. CrossRefGoogle Scholar
  10. Angelino D, Gennari L, Blasa M, Selvaggini R, Urbani S, Esposto S, Servili M, Ninfali P (2011) Chemical and cellular antioxidant activity of phytochemicals purified from olive mill waste waters. J Agric Food Chem 59:2011–2018. CrossRefGoogle Scholar
  11. Auñon-Calles D, Canut L, Visioli F (2013a) Toxicological evaluation of pure hydroxytyrosol. Food Chem Toxicol 55:498–504. CrossRefGoogle Scholar
  12. Auñon-Calles D, Giordano E, Bohnenberger S, Visioli F (2013b) Hydroxytyrosol is not genotoxic in vitro. Pharmacol Res 74:87–93. CrossRefGoogle Scholar
  13. Balestrini R, Gnavi G, Diallinas G, Kostakis IK, Rafailidou N, Kalpaktsi I, Komianou AC, Tsouvali V, Zantza I, Mikros E, Skaltsounis AL (2018) Hydroxytyrosol (HT) analogs act as potent antifungals by direct disruption of the fungal cell membrane. Front Microbiol 9:2624. CrossRefGoogle Scholar
  14. Bellumori M, Cecchi L, Romani A, Mulinacci N, Innocenti M (2018) Recovery and stability over time of phenolic fractions by an industrial filtration system of olive mill wastewaters: a three-year study. J Sci Food Agric 98:2761–2769. CrossRefGoogle Scholar
  15. Ben Sassi A, Boularbah A, Jaouad A, Walker G, Boussaid A (2006) A comparison of olive oil mill wastewaters (OMW) from three different processes in Morocco. Process Biochem 41:74–78. CrossRefGoogle Scholar
  16. Benzie IFF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76. CrossRefGoogle Scholar
  17. Bernath-Levin K, Shainsky J, Sigawi L, Fishman A (2014) Directed evolution of nitrobenzene dioxygenase for the synthesis of the antioxidant hydroxytyrosol. Appl Microbiol Biotechnol 98:4975–4985. CrossRefGoogle Scholar
  18. Bernini R, Mincione E, Barontini M, Crisante F (2008) Convenient synthesis of hydroxytyrosol and its lipophilic derivatives from tyrosol or homovanillyl alcohol. J Agric Food Chem 56:8897–8904. CrossRefGoogle Scholar
  19. Bertin L, Berselli S, Fava F, Petrangeli-Papini M, Marchetti L, Petrangeli-Papinib M, Marchettia L (2004) Anaerobic digestion of olive mill wastewaters in biofilm reactors packed with granular activated carbon and “‘Manville’” silica beads. Water Res 38:3167–3178. CrossRefGoogle Scholar
  20. Bisignano G, Tomaino A, Cascio RL, Crisafi G, Uccella N, Saija A (1999) On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol. J Pharm Pharmacol 51:971–974. CrossRefGoogle Scholar
  21. Bouallagui Z, Sayadi S (2006) Production of high hydroxytyrosol yields via tyrosol conversion by Pseudomonas aeruginosa immobilized resting cells. J Agric Food Chem 54:9906–9911. CrossRefGoogle Scholar
  22. Bouallagui Z, Sayadi S (2018) Bioconversion of tyrosol into hydroxytyrosol under bench-scale fermentation. Biomed Res Int 2018:5. CrossRefGoogle Scholar
  23. Bouaziz M, Sayadi S (2005) Isolation and evaluation of antioxidants from leaves of a Tunisian cultivar olive tree. Eur J Lipid Sci Technol 107:497–504. CrossRefGoogle Scholar
  24. Brooks SJ, Doyle EM, O’Connor KE (2006) Tyrosol to hydroxytyrosol biotransformation by immobilised cell extracts of Pseudomonas putida F6. Enzym Microb Technol 39:191–196. CrossRefGoogle Scholar
  25. Brouk M, Fishman A (2009) Protein engineering of toluene monooxygenases for synthesis of hydroxytyrosol. Food Chem 116:114–121. CrossRefGoogle Scholar
  26. Brouk M, Fishman A (2012) Improving process conditions of hydroxytyrosol synthesis by toluene-4-monooxygenase. J Mol Catal B Enzym 84:121–127. CrossRefGoogle Scholar
  27. Capasso R, Cristinzio G, Evidente A, Scognamiglio F (1992) Isolation, spectroscopy and selective phytotoxic effects of polyphenols from vegetable waste waters. Phytochemistry 31:4125–4128. CrossRefGoogle Scholar
  28. Capasso R, Evidente A, Avolio S, Solla F, Salvatore Avolio A, Solla F (1999) A highly convenient synthesis of hydroxytyrosol and its recovery from agricultural waste waters. J Agric Food Chem 47:1745–1748. CrossRefGoogle Scholar
  29. Carrasco-Pancorbo A, Cerretani L, Bendini A, Segura-Carretero A, Del Carlo M, Gallina-Toschi T, Lercker G, Compagnone D, Fernández-Gutiérrez A (2005) Evaluation of the antioxidant capacity of individual phenolic compounds in virgin olive oil. J Agric Food Chem 53:8918–8925. CrossRefGoogle Scholar
  30. Chen W, Yao J, Meng J, Han W, Tao Y, Chen Y, Guo Y, Shi G, He Y, Jin J-M, Tang S-Y (2019) Promiscuous enzymatic activity-aided multiple-pathway network design for metabolic flux rearrangement in hydroxytyrosol biosynthesis. Nat Commun 10:960. CrossRefGoogle Scholar
  31. Choo HJ, Ji Kim E, Yeon Kim S, Lee Y, Kim B-G, Ahn J-H (2018) Microbial synthesis of hydroxytyrosol and hydroxysalidroside. Appl Biol Chem 61:295–301. CrossRefGoogle Scholar
  32. Christian MS, Sharper VA, Hoberman AM, Seng JE, Fu L, Covell D, Diener RM, Bitler CM, Crea R (2004) The toxicity profile of hydrolyzed aqueous olive pulp extract. Drug Chem Toxicol 27:309–330. CrossRefGoogle Scholar
  33. Chung D, Yeon Kim S, Ahn J-H (2017) Production of three phenylethanoids, tyrosol, hydroxytyrosol, and salidroside, using plant genes expressing in Escherichia coli. Sci Rep 7:2578. CrossRefGoogle Scholar
  34. Couto E, Boffetta P, Lagiou P, Ferrari P, Buckland G, Overvad K, Dahm CC, Tjønneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault M-C, Cottet V, Trichopoulos D, Naska A, Benetou V, Kaaks R, Rohrmann S, Boeing H, von Ruesten A, Panico S, Pala V, Vineis P, Palli D, Tumino R, May A, Peeters PH, Bueno-de-Mesquita HB, Büchner FL, Lund E, Skeie G, Engeset D, Gonzalez CA, Navarro C, Rodríguez L, Sánchez M-J, Amiano P, Barricarte A, Hallmans G, Johansson I, Manjer J, Wirfärt E, Allen NE, Crowe F, Khaw K-T, Wareham N, Moskal A, Slimani N, Jenab M, Romaguera D, Mouw T, Norat T, Riboli E, Trichopoulou A (2011) Mediterranean dietary pattern and cancer risk in the EPIC cohort. Br J Cancer 104:1493–1499. CrossRefGoogle Scholar
  35. Crea R (2002) Method of obtaining a hydroxytyrosol-rich composition from vegetation water. WO 02/18310 A1.
  36. Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 15:7313–7352. CrossRefGoogle Scholar
  37. de Bock M, Derraik JGB, Brennan CM, Biggs JB, Morgan PE, Hodgkinson SC, Hofman PL, Cutfield WS (2013) Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial. PLoS One 8:e57622. CrossRefGoogle Scholar
  38. De Leonardis A, Aretini A, Alfano G, Macciola V, Ranalli G (2008) Isolation of a hydroxytyrosol-rich extract from olive leaves (Olea Europaea L.) and evaluation of its antioxidant properties and bioactivity. Eur Food Res Technol 226:653–659. CrossRefGoogle Scholar
  39. Deffieux D, Gossart P, Quideau S (2014) Facile and sustainable synthesis of the natural antioxidant hydroxytyrosol. Tetrahedron Lett 55:2455–2458. CrossRefGoogle Scholar
  40. Delisi R, Saiano F, Pagliaro M, Ciriminna R (2016) Quick assessment of the economic value of olive mill waste water. Chem Cent J 10:63. CrossRefGoogle Scholar
  41. Di Tommaso D, Calabrese R, Rotilio D (1998) Identification and quantitation of hydroxytyrosol in Italian wines. J High Resolut Chromatogr 21:549–553.<549::AID-JHRC549>3.0.CO;2-Z CrossRefGoogle Scholar
  42. EFSA Panel on dietetic products, nutrition and allergies (2017) Safety of hydroxytyrosol as a novel food pursuant to Regulation (EC) No 258/97. EFSA J 15.
  43. EFSA Panel on dietetic products, nutrition and allergies (2011) Scientific Opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles from oxidative damage (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL cholesterol concentrations (ID 1639), mainte. EFSA J 9.
  44. El-Abbassi A, Hafidi A, García-Payo MC, Khayet M (2009) Concentration of olive mill wastewater by membrane distillation for polyphenols recovery. Desalination 245:670–674. CrossRefGoogle Scholar
  45. Espín JC, Soler-Rivas C, Cantos E, Tomá S-Barberán FA, Wichers HJ (2001) Synthesis of the antioxidant hydroxytyrosol using tyrosinase as biocatalyst. J Agric Food Chem 49:1187–1193. CrossRefGoogle Scholar
  46. Fabiani R, De Bartolomeo A, Rosignoli P, Servili M, Montedoro GF, Morozzi G (2002) Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Eur J Cancer Prev 11:351–358. CrossRefGoogle Scholar
  47. Fernandez-Bolanos J, Heredia Moreno A, Rodriguez Gutierrez G, Rodriguez Acros R, Jimenez Araujo A, Guillen Bejarano R (2002) Method for obtaining purified hydroxytyrosol from products and by-products derived from the olive tree. WO 02/064537 A1. Google Scholar
  48. Fernández-Bolaños J, Rodriguez G, Rodriquez R, Heredia H, Guilen RA, Ana J (2002) Production in large quantities of highly purified hydroxytyrosol from liquid−solid waste of two-phase olive oil processing or “alperujo.” J Agric Food Chem 50:6804–6811 . doi:
  49. Fernandez-Bolanos J, Rodriguez Gutierrez G, Lama Munoz A, Sanchez Moral P (2012) Device and method for processing olive oil production byproducts.  ES 2 374 675 A1.
  50. Fernández-Bolaños JG, López Ó, Ángeles López-García M, Marset A, López-García M, Azucena M (2012) Biological properties of hydroxytyrosol and its derivatives. In: Olive oil-constituents, quality, health properties and bioconversions, pp 375–396Google Scholar
  51. Goldsmith CD, Vuong QV, Stathopoulos CE, Roach PD, Scarlett CJ (2018) Ultrasound increases the aqueous extraction of phenolic compounds with high antioxidant activity from olive pomace. LWT - Food Sci Technol 89:284–290. CrossRefGoogle Scholar
  52. Goldstein DS, Jinsmaa Y, Sullivan P, Holmes C, Kopin IJ, Sharabi Y (2016) 3,4-Dihydroxyphenylethanol (hydroxytyrosol) mitigates the increase in spontaneous oxidation of dopamine during monoamine oxidase inhibition in PC12 cells. Neurochem Res 41:2173–2178. CrossRefGoogle Scholar
  53. Gomez-Acebo E (2015) GRAS Notice (GRN) No. 600 for Seprox hydroxytyrosol.
  54. Gonçalves I, Andersson Georgiadou E, Mattsson S, Skog G, Pedro L, Fernandes E, Fernandes J, Dias N, Engström G, Nilsson J, Stenström K (2015) Direct association between diet and the stability of human atherosclerotic plaque. Sci Rep 5:15524. CrossRefGoogle Scholar
  55. González-Alonso A, Pérez-López P, Varela-López A, Ramírez-Tortosa MC, Battino M, Quiles JL (2015) Experimental evidence on the role of different types of unsaturated fats in the diet on aging. Spanish J Geriatr Gerontol 50:285–288. Google Scholar
  56. González-Correa JA, Navas MD, Lopez-Villodres JA, Trujillo M, Espartero JL, De La Cruz JP (2008) Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia–reoxygenation. Neurosci Lett 446:143–146. CrossRefGoogle Scholar
  57. Granados-Principal S, Quiles JL, Ramirez-Tortosa CL, Sanchez-Rovira P, Ramirez-Tortosa MC (2010) Hydroxytyrosol: from laboratory investigations to future clinical trials. Nutr Rev 68:191–206. CrossRefGoogle Scholar
  58. Gremlnger DC, Burns GP, Lynn S, Hanson DN, King CJ (1982) Solvent extraction of phenols from water. Ind Eng Chem Process Des Dev 21:51–54. CrossRefGoogle Scholar
  59. Halaouli S, Asther M, Kruus K, Guo L, Hamdi M, Sigoillot J-C, Asther M, Lomascolo A (2005) Characterization of a new tyrosinase from Pycnoporus species with high potential for food technological applications. J Appl Microbiol 98:332–343. CrossRefGoogle Scholar
  60. He J, Alister-Briggs M, de Lyster T, Jones GP (2013) Stability and antioxidant potential of purified olive mill wastewater extracts. Food Chem 131:1312–1321CrossRefGoogle Scholar
  61. Hussam Ahmad-Qasem M, Cánovas J, Barrajón-Catalán E, Micol V, Andrés Cárcel J, Vicente García-Pérez J (2013) Kinetic and compositional study of phenolic extraction from olive leaves (var. Serrana) by using power ultrasound. Innov Food Sci Emerg Technol 17:120–129. CrossRefGoogle Scholar
  62. Jeger M, Caffier D, Candresse T, Chatzivassiliou E, Dehnen-Schmutz K, Gilioli G, Grégoire J, Jaques Miret JA, MacLeod A, Navajas Navarro M, Niere B, Parnell S, Potting R, Rafoss T, Rossi V, Urek G, Van Bruggen A, Van der Werf W, West J, Winter S, Almeida R, Bosco D, Jacques M, Landa B, Purcell A, Saponari M, Czwienczek E, Delbianco A, Stancanelli G, Bragard C (2018) Updated pest categorisation of Xylella fastidiosa. EFSA J 16.
  63. Koma D, Yamanaka H, Moriyoshi K, Ohmoto T, Sakai K (2012) Production of aromatic compounds by metabolically engineered Escherichia coli with an expanded shikimate pathway. Appl Environ Microbiol 78:6203–6216. CrossRefGoogle Scholar
  64. Koolen HHF, Pral EMF, Alfieri SC, Marinho JVN, Serain AF, Hernández-Tasco AJ, Andreazza NL, Salvador MJ (2017) Antiprotozoal and antioxidant alkaloids from Alternanthera littoralis. Phytochemistry 134:106–113. CrossRefGoogle Scholar
  65. Leouifoudi I, Zyad A, Amechrouq A, Oukerrou MA, Mouse HA, Mbarki M (2014) Identification and characterisation of phenolic compounds extracted from Moroccan olive mill wastewater. Food Sci Technol 34:249–257. CrossRefGoogle Scholar
  66. Li X, Chen Z, Wu Y, Yan Y, Sun X, Yuan Q (2018) Establishing an artificial pathway for efficient biosynthesis of hydroxytyrosol. ACS Synth Biol 7:647–654. CrossRefGoogle Scholar
  67. Liebgott P-P, Labat M, Casalot L, Amouric A, Lorquin J (2007) Bioconversion of tyrosol into hydroxytyrosol and 3,4-dihydroxyphenylacetic acid under hypersaline conditions by the new Halomonas sp. strain HTB24. FEMS Microbiol Lett 276:26–33. CrossRefGoogle Scholar
  68. Liebgott P-P, Amouric A, Comte A, Tholozan J-L, Lorquin J (2009) Hydroxytyrosol from tyrosol using hydroxyphenylacetic acid-induced bacterial cultures and evidence of the role of 4-HPA 3-hydroxylase. Res Microbiol 160:757–766. CrossRefGoogle Scholar
  69. Liu M, Yong Q, Yu S (2018) Efficient bioconversion of oleuropein from olive leaf extract to antioxidant hydroxytyrosol by enzymatic hydrolysis and high-temperature degradation. Biotechnol Appl Biochem 65:680–689. CrossRefGoogle Scholar
  70. Martínez-González MA, Salas-Salvadó J, Estruch R, Corella D, Fitó M, Ros E (2015) Benefits of the Mediterranean diet: insights from the PREDIMED study. Prog Cardiovasc Dis 58:50–60. CrossRefGoogle Scholar
  71. Medina-Martínez MS, Truchado P, Castro-Ibáñez I, Allende A (2015) Antimicrobial activity of hydroxytyrosol: a current controversy. Biosci Biotechnol Biochem 80:801–810. CrossRefGoogle Scholar
  72. Mulinacci N, Innocenti M, La Marca G, Mercalli E, Giaccherini C, Romani A, Erica S, Vincieri FF (2005) Solid olive residues: insight into their phenolic composition. J Agric Food Chem 53:8963–8969. CrossRefGoogle Scholar
  73. Napora-Wijata K, Robins K, Osorio-Lozada A, Winkler M (2014) Whole-cell carboxylate reduction for the synthesis of 3-hydroxytyrosol. Chem Cat Chem 6:1089–1095. Google Scholar
  74. O’connor KE, Witholt B, Duetz W (2001) p-Hydroxyphenylacetic acid metabolism in Pseudomonas putida F6. J Bacteriol 183:928–933. CrossRefGoogle Scholar
  75. O’Connor K, Molloy S, Davis R, Shaw W (2017) A method for the enzymatic conversion of a phenol substrate into a corresponding catechol product.  US 2017/0355969 A1.
  76. Orenes-Piñero E, García-Carmona F, Sánchez-Ferrer Á (2013) A new process for obtaining hydroxytyrosol using transformed Escherichia coli whole cells with phenol hydroxylase gene from Geobacillus thermoglucosidasius. Food Chem 139:377–383. CrossRefGoogle Scholar
  77. Paiva-Martins F, Ribeirinha T, Silva A, Gonçalves R, Pinheiro V, Mourão JL, Outor-Monteiro D (2014) Effects of the dietary incorporation of olive leaves on growth performance, digestibility, blood parameters and meat quality of growing pigs. J Sci Food Agric 94:3023–3029. CrossRefGoogle Scholar
  78. Paraskeva P, Diamadopoulos E (2006) Technologies for olive mill wastewater (OMW) treatment: a review. J Chem Technol Biotechnol J Chem Technol Biotechnol 81:1475–1485. CrossRefGoogle Scholar
  79. Pastor A, Rodríguez-Morató J, Olesti E, Pujadas M, Pérez-Mañá C, Khymenets O, Fitó M, Covas M-I, Solá R, Motilva M-J, Farré M, de la Torre R (2016) Analysis of free hydroxytyrosol in human plasma following the administration of olive oil. J Chromatogr A 1437:183–190. CrossRefGoogle Scholar
  80. Pérez-Bonilla M, Salido S, van Beek TA, Altarejos J (2014) Radical-scavenging compounds from olive tree ( Olea europaea L.) wood. J Agric Food Chem 62:144–151. CrossRefGoogle Scholar
  81. Piersanti G, Retini M, Espartero JL, Madrona A, Zappia G (2011) An efficient, economical synthesis of hydroxytyrosol and its protected forms via Baeyer-Villiger oxidation. Tetrahedron Lett 52:4938–4940. CrossRefGoogle Scholar
  82. Purcaro G, Codony R, Pizzale L, Mariani C, Conte L (2014) Evaluation of total hydroxytyrosol and tyrosol in extra virgin olive oils. Eur J Lipid Sci Technol 116:805–811. Google Scholar
  83. Robles-Almazan M, Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Rodriguez-Garcia C, Quiles JL, Mc R-T (2018) Hydroxytyrosol: bioavailability, toxicity, and clinical applications. Food Res Int 105:654–667. CrossRefGoogle Scholar
  84. Rubio-Senent F, Rodríguez-Gutíerrez G, Lama-Mun A, Ferna J (2012) New phenolic compounds hydrothermally extracted from the olive oil byproduct alperujo and their antioxidative activities. J Agric Food Chem 60:1175–1186. CrossRefGoogle Scholar
  85. Rubio-Senent F, Fernández-Bolaños J, García-Borrego A, Lama-Muñoz A, Rodríguez-Gutiérrez G (2017) Influence of pH on the antioxidant phenols solubilised from hydrothermally treated olive oil by-product (alperujo). Food Chem 219:339–345. CrossRefGoogle Scholar
  86. Russo C (2007) A new membrane process for the selective fractionation and total recovery of polyphenols, water and organic substances from vegetation waters (VW). J Memb Sci 288:239–246. CrossRefGoogle Scholar
  87. Salas-Salvadó J, Bulló M, Estruch R, Ros E, Covas M-I, Ibarrola-Jurado N, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Romaguera D, Lapetra J, Lamuela-Raventós RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez-González MA (2014) Prevention of diabetes with Mediterranean diets. Ann Intern Med 160:1–10. CrossRefGoogle Scholar
  88. Santos MM, Piccirillo C, Castro PML, Kalogerakis N, Pintado ME (2012) Bioconversion of oleuropein to hydroxytyrosol by lactic acid bacteria. World J Microbiol Biotechnol 28:2435–2440. CrossRefGoogle Scholar
  89. Saponari M, Boscia D, Altamura G, Loconsole G, Zicca S, D’Attoma G, Morelli M, Palmisano F, Saponari A, Tavano D, Savino VN, Dongiovanni C, Martelli GP (2017) Isolation and pathogenicity of Xylella fastidiosa associated to the olive quick decline syndrome in southern Italy. Sci Rep 7:17723. CrossRefGoogle Scholar
  90. Satoh Y, Tajima K, Munekata M, Keasling JD, Lee TS (2012) Engineering of L-tyrosine oxidation in Escherichia coli and microbial production of hydroxytyrosol. Metab Eng 14:603–610. CrossRefGoogle Scholar
  91. Schöpf C, Göttmann G, Meisel E-M, Neuroth† L (1949) Synthesis of 3,4-diyhydroxyphenylethanol. European J Org Chem 563:86–93 . doi:
  92. Shakeri P, Durmic Z, Vadhanabhuti J, Vercoe PE (2017) Products derived from olive leaves and fruits can alter in vitro ruminal fermentation and methane production. J Sci Food Agric 97:1367–1372. CrossRefGoogle Scholar
  93. Soni M, Burdock G, Christian M, Bitler C, Crea R (2006) Safety assessment of aqueous olive pulp extract as an antioxidant or antimicrobial agent in foods. Food Chem Toxicol 44:903–915. CrossRefGoogle Scholar
  94. Soto ML, Moure A, Domínguez H, Parajó JC (2011) Recovery, concentration and purification of phenolic compounds by adsorption: a review. J Food Eng 105:1–27. CrossRefGoogle Scholar
  95. Trantas E, Navakoudis E, Pavlidis T, Nikou T, Halabalaki M, Skaltsounis L, Ververidis F (2019) Dual pathway for metabolic engineering of E. coli metabolism to produce the highly valuable hydroxytyrosol. BioRxiv:536458.
  96. Xie P, Huang L, Zhang C, Deng Y, Wang X, Cheng J (2019) Enhanced extraction of hydroxytyrosol, maslinic acid and oleanolic acid from olive pomace: process parameters, kinetics and thermodynamics, and greenness assessment. Food Chem 276:662–674. CrossRefGoogle Scholar
  97. Yangui A, Abderrabba M (2018) Towards a high yield recovery of polyphenols from olive mill wastewater on activated carbon coated with milk proteins: experimental design and antioxidant activity. Food Chem 262:102–109. CrossRefGoogle Scholar
  98. Zagklis DP, Paraskeva CA (2018) Isolation of organic compounds with high added values from agro-industrial solid wastes. J Environ Manag 216:183–191. CrossRefGoogle Scholar
  99. Ziosi P, Paolucci C, Santarelli F, Tabanelli T, Passeri S, Cavani F, Righi P (2018) A two-step process for the synthesis of hydroxytyrosol. ChemSusChem 11:1–10. CrossRefGoogle Scholar
  100. Zulueta A, Esteve MJ, Frígola A (2009) Analytical methods ORAC and TEAC assays comparison to measure the antioxidant capacity of food products. Food Chem 114:310–316. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • James Britton
    • 1
  • Reeta Davis
    • 1
  • Kevin E. O’Connor
    • 1
    • 2
    Email author
  1. 1.School of Biomolecular and Biomedical ScienceUniversity College DublinDublin 4Ireland
  2. 2.Beacon Bioeconomy Research CentreUniversity College DublinDublin 4Ireland

Personalised recommendations