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Phytochemistry Reviews

, Volume 14, Issue 5, pp 727–743 | Cite as

Nutritionally important carotenoids as consumer products

  • Judit Berman
  • Uxue Zorrilla-López
  • Gemma Farré
  • Changfu Zhu
  • Gerhard Sandmann
  • Richard M. Twyman
  • Teresa Capell
  • Paul Christou
Article

Abstract

Carotenoids are nutritionally-beneficial organic tetraterpenoid pigments synthesized mainly by plants, bacteria and fungi. Although research has focused on the production of carotenoids in staple crops to improve nutritional welfare in developing countries, there is also an enormous market for carotenoids in the industrialized world, where they are produced both as commodities and luxury goods targeted at the pharmaceutical, nutraceutical, food/feed additive, cosmetics and fine chemicals sectors. Carotenoids are economically valuable because they have diverse bioactive and chemical properties. Some are essential nutrients (e.g. β-carotene), others are antioxidants with specific roles (e.g. lutein and zeaxanthin) or general health-promoting roles that reduce the risk or progression of diseases associated with oxidative stress (e.g. lycopene), and still others are natural pigments (e.g. astaxanthin, which is added to fish feed to impart a desirable pink flesh color). Even carotenoid degradation products, such as damascones and damascenones, are used as fragrances in the perfumes industry. Here we discuss the importance of carotenoids in different market sectors, review current methods for commercial production and its regulation, summarize the most relevant patents and consider evidence supporting the health claims made by different industry sectors, focusing on case studies representing the most commercially valuable carotenoids on the market: β-carotene, lycopene, lutein, zeaxanthin and astaxanthin.

Keywords

Health claims Intellectual property Market production Nutraceuticals Regulation 

Abbreviations

CAGR

Compound annual growth rate

CBFD

Carotenoid β-ring 4-dehydrogenase

CRTISO

Carotenoid isomerase

DMAPP

Dimethylallyl diphosphate

DSHEA

Dietary supplement health and education act

EFSA

European food safety authority

FDA

Food and drug administration

GGPP

Geranyl geranyl diphosphate

GGPPS

Geranyl geranlyl diphosphate synthase

HBFD

4-Hydroxy-β-ring 4-dehydrogenase

HYDB

β-Carotene hydroxylase

IPP

Isopentenyl diphosphate

LYCB

Lycopene β-cyclase

LYCE

Lycopene ɛ-cyclase

MEP

Methylerythritol 4-phosphate

PDS

Pytoene desaturase

PSY

Phytoene synthase

USPTO

United States patent and trademark office

VAD

Vitamin A deficiency

ZDS

ζ-Carotene desaturase

Z-ISO

ζ-Carotene isomerase

Notes

Acknowledgments

Research at the Universitat de Lleida is supported by the Ministerio de Ciencia e Innovación (Grants No. BIO2011-23324, BIO02011-22525, PIM2010PKB-0074, European Research Council IDEAS Advanced Grant Program (BIOFORCE) (to PC); ERC-2013-PoC 619161 (to PC); European Cooperation in Science and Technology (COST Action FA0804); and RecerCaixa.

Conflict of interest

The authors have declared that no competing interests exist.

Supplementary material

11101_2014_9373_MOESM1_ESM.doc (1014 kb)
Supplementary material 1 (DOC 1013 kb)
11101_2014_9373_MOESM2_ESM.docx (11 kb)
Supplementary material 2 (DOCX 11 kb)

References

  1. Abdullaev FI (2002) Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus). Exp Biol Med 227:20–25Google Scholar
  2. Altincicek B, Kovacs JL, Gerardo NM (2012) Horizontally transferred fungal carotenoid genes in the two-spotted spider mite Tetranychus urticae. Biol Lett 8:253–257PubMedCentralPubMedCrossRefGoogle Scholar
  3. Anunciato TP, da Rocha Filho PA (2012) Carotenoids and polyphenols in nutricosmetics, nutraceuticals, and cosmeceuticals. J Cosmet Dermatol 11:51–54PubMedCrossRefGoogle Scholar
  4. Aoki H, Kieu NT, Kuze N et al (2002) Carotenoid pigments in GAC fruit (Momordica cochinchinensis SPRENG). Biosci Biotechnol Biochem 66:2479–2482PubMedCrossRefGoogle Scholar
  5. Auldridge ME, McCarty DR, Klee HJ (2006) Plant carotenoid cleavage oxygenases and their apocarotenoid products. Curr Opin Plant Biol 9:315–321PubMedCrossRefGoogle Scholar
  6. Bai C, Twyman RM, Farré G et al (2011) A golden era—pro-vitamin A enhancement in diverse crops. In vitro Cell Dev Biol Plant 47:205–221CrossRefGoogle Scholar
  7. Bathaie SZ, Mousavi SZ (2010) New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr 8:761–786CrossRefGoogle Scholar
  8. Ben-Amotz A, Katz A, Avron M (1982) Accumulation of β-carotene in halotolerant algae: purification and characterization of β-carotene-rich globules from Dunaliella bardawil (Chlorophyceae). J Phycol 18:529–537CrossRefGoogle Scholar
  9. Berman J, Zhu C, Pérez-Massot E et al (2013) Can the world afford to ignore biotechnology solutions that address food insecurity? Plant Mol Biol 83:5–19PubMedCrossRefGoogle Scholar
  10. Bernhard K, Müller RK, Spruijtenburg R (1984) Process for the preparation of astaxanthin and intermediates in the astaxanthin synthesis. Eur Patent EP0101597Google Scholar
  11. Bhosale P, Bernstein PS (2005) Microbial xanthophylls. Appl Microbiol Biotechnol 68:445–455PubMedCrossRefGoogle Scholar
  12. Boussiba S, Vonshak A (1991) Astaxanthin accumulation in the green alga Haematococcus pluvialis. Plant Cell Physiol 32:1077–1082Google Scholar
  13. Bouvier F, Suire C, Mutterer J et al (2003) Oxidative remodeling of chromoplast carotenoids: identification of the carotenoid dioxygenase CsCCD and CsZCD genes involved in crocus secondary metabolite biogenesis. Plant Cell 15:47–62PubMedCentralPubMedCrossRefGoogle Scholar
  14. Bramley PM (2000) Is lycopene beneficial to human health? Phytochemistry 54:233–236PubMedCrossRefGoogle Scholar
  15. Breitenbach J, Sandmann G (2005) ζ-Carotene cis isomers as products and substrates in the plant poly-cis carotenoid biosynthetic pathway to lycopene. Planta 220:785–793PubMedCrossRefGoogle Scholar
  16. Britton G, Liaaen Jensen S, Pfander H (2004) Carotenoids handbook. Birkauser, BaselCrossRefGoogle Scholar
  17. Capell T, Christou P (2004) Progress in plant metabolic engineering. Curr Opin Biotechnol 15:148–154PubMedCrossRefGoogle Scholar
  18. Chappell J (1995) Biochemistry and molecular biology of the isoprenoid biosynthetic pathway in plants. Ann Rev Plant Physiol Plant Mol Biol 46:521–547CrossRefGoogle Scholar
  19. Chen Y, Li F, Wurtzel ET (2010) Isolation and characterization of the ZISO gene encoding a missing component of carotenoid biosynthesis in plants. Plant Physiol 153:66–79PubMedCentralPubMedCrossRefGoogle Scholar
  20. Chew BP, Park JS, Wong MW et al (1999) A comparison of the anticancer activities of dietary β-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res 19:1849–1853PubMedGoogle Scholar
  21. Commission Directive 87/552/EECC amending the Annexes to Council Directive 70/524/EEC concerning additives in feedingstuffs (2004). Official J EEUU, 30.04.2004Google Scholar
  22. Commission Regulation (EC) No 1170/2009 of 30 November 2009 amending Directive 2002/46/EC of the European Parliament and of Council and Regulation (EC) No 1925/2006 of the European Parliament and of the Council as regards the lists of vitamin and mineral and their forms that can be added to foods, including food supplements. Official J EEUU, 01.12.2009Google Scholar
  23. Commission Regulation (EC) No 1288/2004 of 12 July 2004 concerning the permanent authorization of certain additives and the provisional authorization of a new use of an additive already authorized in feedingstuffs. Official J EEUU, 14 July 2004Google Scholar
  24. Commission Regulation (EC) No 393/2008 of 30 April 2008 concerning the authorization of astaxanthin dimethylsdisuccinate as a feed additive. Official J EEUU, 01.05.2008Google Scholar
  25. Commission Regulation (EC) No 721/2008 of 25 July 2008 concerning the authorization of a preparation of red carotenoid-rich bacterium Paracoccus carotinifaciens as a feed additive. Official J EEUU, 26.07.2008Google Scholar
  26. Commission Regulation (EC) No 880/2004 of 29 April 2004 authorising without time limit the use of beta-carotene and canthaxanthin as additives in feeding-stuffs belonging to the group of colouring matters including pigments. Official J EEUU, 30.04.2004Google Scholar
  27. Commission Regulation (EU) No 1129/2011 of 11 November 2011 amending Annexx II to Regulation (EC) No 1333/2008 of the European Parliament and of the Council. Official J EEUU, 12.11.2011Google Scholar
  28. Commission Regulation (EU) No 231/2012 of 9 March 2012 laying down specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council. Official J EEUU, 22.03.2012Google Scholar
  29. Cunningham FX, Gantt E (2011) Elucidation of the pathway to astaxanthin in the flowers of Adonis aestivalis. Plant Cell 23:3055–3069PubMedCentralPubMedCrossRefGoogle Scholar
  30. Cunningham FX, Pogson B, Sun Z, McDonald KA, DellaPenna D, Gantt E (1996) Functional analysis of the β and ε lycopene cyclase enzymes of Arabidopsis reveals a mechanism for control of cyclic carotenoid formation. Plant Cell 8:1613–1626PubMedCentralPubMedGoogle Scholar
  31. Dawson TL (2009) Biosynthesis and synthesis of natural colours. Color Technol 125:61–73CrossRefGoogle Scholar
  32. Diplock AT, Charleux JL, Crozier-Willi G et al (1998) Functional food science and defence against reactive oxidative species. Br J Nutr 80:S77–S112PubMedCrossRefGoogle Scholar
  33. Draelos ZD (2010) Nutrition and enhancing youthful-appearing skin. Clin Dermatol 28:400–408PubMedCrossRefGoogle Scholar
  34. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2010) Scientific Opinion on the substantiation of health claims related to vitamin A (including β-carotene) and maintenance of normal vision (ID 4239, 4701), maintenance of normal skin and mucous membranes (ID 4660, 4702), and maintenance of normal hair (ID 4660) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 8:1754–1767Google Scholar
  35. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2011a) Scientific Opinion on the substantiation of a health claim related to lutein in combination with zeaxanthin, and maintenance of normal vision (ID 1606) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 9:2039–2053Google Scholar
  36. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2011b) Scientific Opinion on the substantiation of health claims related to lycopene and protection of DNA, proteins and lipids from oxidative damage (ID 1608, 1609, 1611, 1662, 1663(1664), 1899, 1942. 2081, 2082, 2142, 2374), protection of the skin from UV-induced (including photo-oxidative) damage (ID 1259, 1607, 1665, 2143, 2262, 2373), contribution to normal cardiac function (ID 1610, 2372), and maintenance of normal vision (ID 1827) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 9:2031–2059Google Scholar
  37. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2011c) Scientific Opinion on the substantiation of health claims related to astaxanthin and protection of the skin from UV-induced damage (ID 1687, 1979), defence against Helicobacter pylori (ID 1686), contribution to normal spermatogenesis (ID 1688), contribution to normal muscle function (ID 1685), and “immune system” (ID 1689, 1919, 1980) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 9:2206–2224Google Scholar
  38. Ernst H (2002) Recent advances in industrial carotenoid synthesis. Pure Appl Chem 74:2213–2226CrossRefGoogle Scholar
  39. Farré G, Sanahuja G, Naqvi S et al (2010) Travel advice on the road to carotenoids in plants. Plant Sci 179(28):48Google Scholar
  40. Farré G, Bai C, Twyman RM et al (2011) Nutritious crops producing multiple carotenoids—a metabolic balancing act. Trends Plant Sci 16:532–540PubMedCrossRefGoogle Scholar
  41. Farré G, Rivera SM, Alves R et al (2013) Targeted transcriptomic and metabolic profiling reveals temporal bottlenecks in the maize carotenoid pathway that may be addressed by multigene engineering. Plant J 75:441–455PubMedCrossRefGoogle Scholar
  42. Fassett RG, Coombes JS (2005) Astaxanthin: a potential therapeutic agent in cardiovascular disease. Mar Drugs 9:447–465CrossRefGoogle Scholar
  43. Fassett RG, Coombes JS (2012) Astaxanthin in cardiovascular health and disease. Molecules 17:2030–2048PubMedCrossRefGoogle Scholar
  44. FDA (2009) Guidance for industry: a food labeling guide (11. Appendix C: health claims) http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/LabelingNutrition/ucm064919.htm
  45. Franceschi S, Bidoli E, La Vecchia C et al (1994) Tomatoes and risk of digestive-tract cancers. Int J Cancer 59:181–184PubMedCrossRefGoogle Scholar
  46. Fraser PD, Bramley PM (2004) The biosynthesis and nutritional uses of carotenoids. Prog Lipid Res 43:228–265PubMedCrossRefGoogle Scholar
  47. Fraser PD, Romer S, Shipton CA et al (2002) Evaluation of transgenic tomato plants expressing an additional phytoene synthase in a fruit-specific manner. Proc Natl Acad Sci USA 99:1092–1097PubMedCentralPubMedCrossRefGoogle Scholar
  48. Frusciante L, Carli P, ERcolano MR et al (2007) Antioxidant nutritional quality of tomato. Mol Nutr Food Res 51:609–617PubMedCrossRefGoogle Scholar
  49. Garcia E, Barrett DM (2006) Assessing lycopene content in California processing tomatoes. J Food Process Preserv 30:56–70CrossRefGoogle Scholar
  50. Gassel S, Schewe H, Schmidt I et al (2013) Multiple improvement of astaxanthin biosynthesis in Xanthophyllomyces dendrorhous by a combination of conventional mutagenesis and metabolic pathway engineering. Biotechnol Lett 35:565–569PubMedCrossRefGoogle Scholar
  51. Giovannucci E, Ascherio A, Rimm EB et al (1995) Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87:1767–1776PubMedCrossRefGoogle Scholar
  52. Gua ZX, Chen DM, Han YB et al (2008) Optimization of carotenoids extraction from Rhodobacter sphaeroides. LWT-Food Sci Technol 41:1082–1088CrossRefGoogle Scholar
  53. Hammond BR Jr, Johnson EJ, Russel RM et al (1997) Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci 38:1795–1801PubMedGoogle Scholar
  54. Hensel A, Rösing M (2003) Crocus. In: Blaschek W, Ebel S, Hackenthal E, Holzgrabe U, Keller K, Reichling J (eds) HagerRom: Hagers Handbuch der Drogen und Arzneistoffe. Springer Electronic Media, HeidelbergGoogle Scholar
  55. Huang JC, Zhong YJ, Liu J, Sandmann G et al (2013) Metabolic engineering of tomato for high-yield production of astaxanthin. Metab Eng 17:59–67PubMedCrossRefGoogle Scholar
  56. Isaacson T, Ohad I, Beyer P et al (2004) Analysis in vitro of the enzyme CRTISO establishes a poly-cis-carotenoid biosynthesis pathway in plants. Plant Physiol 136:4246–4255PubMedCentralPubMedCrossRefGoogle Scholar
  57. Iwamoto T, Hosoda K, Hirano R et al (2000) Inhibition of low-density lipoprotein oxidation by astaxanthin. J Atheroscler Thromb 7:216–222PubMedCrossRefGoogle Scholar
  58. Jaswir I, Noviendri D, Hasrini RF et al (2011) Carotenoids: sources, medicinal properties and their application in food and nutraceutical industry. J Med Plants Res 5:7119–7131Google Scholar
  59. Jayaraj J, Devlin R, Punja Z (2008) Metabolic engineering of novel ketocarotenoid production in carrot plants. Transgenic Res 17:489–501PubMedCrossRefGoogle Scholar
  60. Jin E, Feth B, Melis A (2003) A mutant of the green alga Dunaliella salina constitutively accumulates zeaxanthin under all growth conditions. Biotechnol Bioeng 8:115–124CrossRefGoogle Scholar
  61. Johnson EA, An GH (1991) Astaxanthin from microbial sources. Crit Rev Biotechnol 11:297–326CrossRefGoogle Scholar
  62. Jyonouchi H, Sun S, Tomita Y et al (1995) Astaxanthin, a carotenoid without vitamin A activity, augments antibody responses in cultures including T-helper cell clones and suboptimal doses of antigen. J Nutr 125:2483–2492PubMedGoogle Scholar
  63. Kang EK, Campbell RE, Bastian E et al (2010) Invited review: annatto usage and bleaching in dairy foods. J Dairy Sci 93:3891–3901PubMedCrossRefGoogle Scholar
  64. Kim J, Smith JJ, Tian L et al (2009) The evolution and function of carotenoid hydroxylases in Arabidopsis. Plant Cell Physiol 50:463–479PubMedCrossRefGoogle Scholar
  65. Knekt P, Reunanen A, Jarvinen R et al (1994) Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol 139:1180–1189PubMedGoogle Scholar
  66. Krinsky NI (1998) Overview of lycopene, carotenoids, and disease prevention. Proc Soc Exp Biol Med 218:95–97PubMedCrossRefGoogle Scholar
  67. Lamers PP, Janssen M, De Vos RC et al (2008) Exploring and exploiting carotenoid accumulation in Dunaliella salina for cell-factory applications. Trends Biotechnol 26:631–638PubMedCrossRefGoogle Scholar
  68. Landrum JT, Bone RA (2001) Lutein, zeaxanthin, and the macular pigment. Arch Biochem Biophys 385:28–40PubMedCrossRefGoogle Scholar
  69. Lemmens L, Colle IJ, Van Buggenhout S et al (2011) Quantifying the influence of thermal process parameters on in vitro β-carotene bioaccessibility: a case study on carrots. J Agric Food Chem 59:3162–3167PubMedCrossRefGoogle Scholar
  70. Li F, Murillo C, Wurtzel ET (2007) Maize Y9 encodes a product essential for 15-cis-zeta-carotene isomerization. Plant Physiol 144:1181–1189PubMedCentralPubMedCrossRefGoogle Scholar
  71. Li Q, Farré G, Naqvi S et al (2010) Cloning and functional characterization of the maize carotenoid isomerase and β-carotene hydroxylase genes and their regulation during endosperm maturation. Transgenic Res 19:1053–1068PubMedCrossRefGoogle Scholar
  72. Mills PK, Beeson WL, Phillips RL et al (1989) Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64:598–604PubMedCrossRefGoogle Scholar
  73. Minguez-Mosquera MI, Hornero-Mendez D (1994) Comparative study of the effect of paprika processing on the carotenoids in pepper (Capsicum annuum) of the Bola and Agridulce varieties. Food Chem 42:1555–1560CrossRefGoogle Scholar
  74. Misawa N, Truesdale MR, Sandmann G et al (1994) Expression of a tomato cDNA coding for phytoene synthase in Escherichia coli, phytoene formation in vivo and in vitro, and functional analysis of the various truncated gene products. J Biochem 116:980–985PubMedGoogle Scholar
  75. Misawa N, Satomi Y, Kondo K et al (1995) Structure and functional analysis of a marine bacterial carotenoid biosynthesis gene cluster and astaxanthin biosynthetic pathway proposed at the gene level. J Bacteriol 177:6575–6584PubMedCentralPubMedGoogle Scholar
  76. Moran NA, Jarvik T (2010) Lateral transfer of genes from fungi underlies carotenoid production in aphids. Science 328:624–627PubMedCrossRefGoogle Scholar
  77. Mozaffarieh M, Sacu S, Wedrich A (2003) The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence. Nutr J 11:20–28CrossRefGoogle Scholar
  78. Mustafa A, Trevino ML, Turner C (2012) Pressurized hot ethanol extraction of carotenoids from carrot by-products. Molecules 17:1809–1818PubMedCrossRefGoogle Scholar
  79. Nadolski G, Cardounel AJ, Zweier JL, Lockwood SF (2006) The synthesis and aqueous superoxide anion scavenging of water-dispersible lutein esters. Bioorg Med Chem Lett 16:775–781PubMedCrossRefGoogle Scholar
  80. Nanou K, Roukas T, Papadakis E (2012) Improved production of carotenes from synthetic medium by Blakeslea trispora in a bubble column reactor. Biochem Eng J 67:203–207CrossRefGoogle Scholar
  81. Naqvi S, Zhu C, Farré G et al (2009) Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways. Proc Natl Acad Sci USA 106:7762–7767PubMedCentralPubMedCrossRefGoogle Scholar
  82. Naqvi S, Zhu C, Farré G et al (2011) Synergistic metabolism in hybrid corn indicates bottlenecks in the carotenoid pathway and leads to the accumulation of extraordinary levels of the nutritionally important carotenoid zeaxanthin. Plant Biotechnol J 9:384–393PubMedCrossRefGoogle Scholar
  83. Nishino H, Murakoshi M, Tokuda H et al (2009) Cancer prevention by carotenoids. Arch Biochem Biophys 483:165–168PubMedCrossRefGoogle Scholar
  84. OJEC (2006) Official Journal of the European Commision of 23 October 2006 authorising the placing on the market of lycopene from Blakeslea trispora as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council. L 296/13Google Scholar
  85. OJEC (2009a) Official Journal of the European Commision of 23 April 2009 authorising the placing on the market of lycopene as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council. L 106/55Google Scholar
  86. OJEC (2009b) Official Journal of the European Commision of 28 April 2009 authorising the placing on the market of lycopene from Blakeslea trispora as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council. L 111/31Google Scholar
  87. OJEC (2009c) Official Journal of the European Commision of 28 April 2009 authorising the placing on the market of lycopene oleoresin from tomatoes as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council. L 109/47Google Scholar
  88. OJEC (2009d) Official Journal of the European Commision of 30 April October 2009 authorising the placing on the market of lycopene as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council. L 110/54Google Scholar
  89. Paine JA, Shipton CA, Chaggar S et al (2005) Improving the nutritional value of Golden Rice through increased pro-vitamin A content. Nat Biotechnol 23:482–487PubMedCrossRefGoogle Scholar
  90. Pashkow FJ, Watumull DG, Campbell CL (2008) Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol 101:58D–68DPubMedCrossRefGoogle Scholar
  91. Pérez-Massot E, Banakar R, Gómez-Galera S et al (2013) The contribution of transgenic plants to better health through improved nutrition: opportunities and constraints. Genes Nutr 8:29–41PubMedCentralPubMedCrossRefGoogle Scholar
  92. Pommer H, Thieme PC (1983) Industrial applications of the Wittig reaction. Top Curr Chem 109(165–188):166Google Scholar
  93. PRweb: Global Carotenoids Mark.et to Reach US$1.3 Billion by 2017, According to a New Report by Global Industry Analysts, Inc. http://www.prweb.com/releases/carotenoids/astaxanthin_beta_carotene/prweb8849957.htm
  94. Quackenbush FW, Firch JG, Brunson AM et al (1963) Carotenoid, oil, and tocopherol content of corn inbreds. Cereal Chem 40:250–253Google Scholar
  95. Raja R, Hemaiswarya S, Rengasamy R (2007) Exploitation of Dunaliella for beta-carotene production. Appl Microbiol Biotechnol 74:517–523PubMedCrossRefGoogle Scholar
  96. Rao LG, Guns E, Rao AV (2003) Lycopene: its role in human health and disease. AGROFood Industry Hi-TechGoogle Scholar
  97. Regulation (EC) No. 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. Official J EEUU, 22.12.2009Google Scholar
  98. Regulation (EC) No. 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. Official J EEUU, 30.12.2006Google Scholar
  99. Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997 concerning novel foods and novel food ingredients. Official J EEUU, 14.07.1997Google Scholar
  100. Rice-Evans CA, Sampson J, Bramley PM et al (1997) Why do we expect carotenoids to be antioxidants in vivo? Free Radic Res 26:381–398PubMedCrossRefGoogle Scholar
  101. Rivera-Madrid R, Escobedo-Medrano RM, Balam-Galera E et al (2006) Preliminary studies toward genetic improvement of annatto (Bixa orellana L.). Sci Hortic 109:165–172CrossRefGoogle Scholar
  102. Rodriguez-Amaya DB, Kimura M, Godoy HT et al (2008) Updated Brazilian database on food carotenoids: factors affecting carotenoid composition. J Food Compos Anal 21:445–463CrossRefGoogle Scholar
  103. Rodriguez-Concepcion M (2006) Early steps in isoprenoid biosynthesis: multilevel regulation of the supply of common precursors in plant cells. Phytochem Rev 5:1–15CrossRefGoogle Scholar
  104. Rüttimann A (1999) Dienolether condensations—a powerful tool in carotenoid synthesis. Pure Appl Chem 71:2285–2293CrossRefGoogle Scholar
  105. Sanahuja G, Farré G, Berman J et al (2013) A question of balance—achieving appropriate nutrient levels in biofortified staple crops. Nutr Res Rev 26:235–245PubMedCrossRefGoogle Scholar
  106. Scaife MA, Ma CA, Ninlayarn T et al (2012) Comparative analysis of β-carotene hydroxylase genes for astaxanthin biosynthesis. J Nat Prod 22:1117–1124CrossRefGoogle Scholar
  107. Schmidt I, Schewe H, Gassel G et al (2011) Biotechnological production of astaxanthin with Phaffia rhodozyma/Xanthophyllomyces dendrorhous. Appl Microbiol Biotechnol 89:555–571PubMedCrossRefGoogle Scholar
  108. Seo M, Koshiba T (2002) Complex regulation of ABA biosynthesis in plants. Trends Plant Sci 7:41–48PubMedCrossRefGoogle Scholar
  109. Shewmaker CK, Sheehy JA, Daley M et al (1999) Seed-specific overexpression of phytoene synthase: increase in carotenoids and other metabolic effects. Plant J 20:401–412PubMedCrossRefGoogle Scholar
  110. Shi XM, Jiang Y, Chen F (2002) High-yield production of lutein by the green microalga Chlorella protothecoides in heterotrophic fed-batch culture. Biotechnol Prog 18:723–727PubMedCrossRefGoogle Scholar
  111. Simkin AJ, Moreau H, Kuntz M et al (2008) An investigation of carotenoid biosynthesis in Coffea canephora and Coffea arabica. J Plant Physiol 165:1087–1106PubMedCrossRefGoogle Scholar
  112. Sommerburg O, Keunen JEE, Bird AC et al (1998) Fruits and vegetables that are source of lutein and zeaxanthin: the macular pigment in human eye. Br J Ophthalmol 82:907–910PubMedCentralPubMedCrossRefGoogle Scholar
  113. Soroka IM, Narushin VG, Turivansky YD et al (2012) Spectroscopy analysis for simultaneous determination of lycopene and β-carotene in fungal biomass of Blakeslea trispora. Acta Biochim Pol 59:65–69PubMedGoogle Scholar
  114. Suseela MR, Toppo K (2006) Haematococcus pluvialis—a green alga, richest natural source of astaxanthin. Curr Sci 90:1602–1603Google Scholar
  115. Tanaka T, Morishita Y, Suzui M et al (1994) Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin. Carcinogenesis 15:15–19PubMedCrossRefGoogle Scholar
  116. Tsao R, Yang R, Young JC et al (2004) Separation of geometric isomers of native lutein diesters in marigold (Tagetes erecta L.) by high-performance liquid chromatography–mass spectrometry. J Chromatogr A 1045:65–70PubMedCrossRefGoogle Scholar
  117. Van Poppel G (1996) Epidemiological evidence for beta-carotene in prevention of cancer and cardiovascular disease. Eur J Clin Nutr 50:S57–S61PubMedGoogle Scholar
  118. Widmer E, Zell R, Broger EA et al (1981) Technische Verfahren zur Synthese von Carotenoiden und verwandten Verbindungen aus 6-oxo-isophoron. II. Ein neues Konzept für die Synthese von (3RS, 3′RS)-astaxanthin. Helv Chim Acta 64:2436–2446CrossRefGoogle Scholar
  119. Yu D, Lydiate DJ, Young LW et al (2008) Enhancing the carotenoid content of Brassica napus seeds by downregulating lycopene epsilon cyclase. Transgenic Res 17:573–585PubMedCrossRefGoogle Scholar
  120. Zhang XW, Gong XD, Chen F (1999) Kinetic models for astaxanthin production by high cell density mixotrophic culture of the microalga Haematococcus pluvialis. J Ind Microbiol Biotech 23:691–696CrossRefGoogle Scholar
  121. Zhu C, Naqvi S, Gómez-Galera S et al (2007) Transgenic Strategies for the nutritional enhancement of plants. Trends Plant Sci 12:548–555 Google Scholar
  122. Zhu C, Naqvi S, Breitenbach J et al (2008) Combinatorial genetic transformation generates a library of metabolic phenotypes for the carotenoid pathway in corn. Proc Natl Acad Sci USA 105:18232–18237PubMedCentralPubMedCrossRefGoogle Scholar
  123. Zhu C, Naqvi S, Capell T et al (2009) Metabolic engineering of ketocarotenoid biosynthesis in higher plants. Arch Biochem Biophys 483:182–190PubMedCrossRefGoogle Scholar
  124. Zhu C, Bai C, Sanahuja G et al (2010) The regulation of carotenoid pigmentation in flowers. Arch Biochem Biophys 504:132–141PubMedCrossRefGoogle Scholar
  125. Zhu C, Sanahuja G, Yuan D et al (2013) Biofortification of plants with altered antioxidant content and composition: genetic engineering strategies. Plant Biotechnol J 11:129–141PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Judit Berman
    • 1
  • Uxue Zorrilla-López
    • 1
  • Gemma Farré
    • 1
    • 2
  • Changfu Zhu
    • 1
  • Gerhard Sandmann
    • 3
  • Richard M. Twyman
    • 4
  • Teresa Capell
    • 1
  • Paul Christou
    • 1
    • 5
  1. 1.Department of Plant Production and Forestry Science, ETSEAUniversity of Lleida-Agrotecnio CenterLleidaSpain
  2. 2.Department of Metabolic BiologyJohn Innes CentreNorwichUK
  3. 3.Biosynthesis Group, Molecular BiosciencesJohann Wolfgang Goethe UniversitätFrankfurtGermany
  4. 4.TRM LtdYorkUK
  5. 5.Institució Catalana de Recerca i Estudis AvançatsBarcelonaSpain

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