Applied Microbiology and Biotechnology

, Volume 89, Issue 3, pp 555–571

Biotechnological production of astaxanthin with Phaffia rhodozyma/Xanthophyllomyces dendrorhous

  • Isabell Schmidt
  • Hendrik Schewe
  • Sören Gassel
  • Chao Jin
  • John Buckingham
  • Markus Hümbelin
  • Gerhard Sandmann
  • Jens Schrader


The oxygenated β-carotene derivative astaxanthin exhibits outstanding colouring, antioxidative and health-promoting properties and is mainly found in the marine environment. To satisfy the growing demand for this ketocarotenoid in the feed, food and cosmetics industries, there are strong efforts to develop economically viable bioprocesses alternative to the current chemical synthesis. However, up to now, natural astaxanthin from Haematococcus pluvialis, Phaffia rhodozyma or Paracoccus carotinifaciens has not been cost competitive with chemically synthesized astaxanthin, thus only serving niche applications. This review illuminates recent advances made in elucidating astaxanthin biosynthesis in P. rhodozyma. It intensely focuses on strategies to increase astaxanthin titers in the heterobasidiomycetous yeast by genetic engineering of the astaxanthin pathway, random mutagenesis and optimization of fermentation processes. This review emphasizes the potential of P. rhodozyma for the biotechnological production of astaxanthin in comparison to other natural sources such as the microalga H. pluvialis, other fungi and transgenic plants and to chemical synthesis.


Astaxanthin Astaxanthin biosynthesis Astaxanthin synthase Bioprocess engineering Metabolic engineering Phaffia rhodozyma 


  1. Acheampong EA, Martin AM (1995) Kinetic studies on the yeast Phaffia rhodozyma. J Basic Microbiol 35(3):147–155CrossRefGoogle Scholar
  2. Alcaíno J, Barahona S, Carmona M, Lozano C, Marcoleta A, Niklitschek M, Sepulveda D, Baeza M, Cifuentes V (2008) Cloning of the cytochrome P450 reductase (crtR) gene and its involvement in the astaxanthin biosynthesis of Xanthophyllomyces dendrorhous. BMC Microbiol 8:169CrossRefGoogle Scholar
  3. Álvarez V, Rodriguez-Saiz M, de la Fuente JL, Gudina EJ, Godio RP, Martin JF, Barredo JL (2006) The crtS gene of Xanthophyllomyces dendrorhous encodes a novel cytochrome-P450 hydroxylase involved in the conversion of beta-carotene into astaxanthin and other xanthophylls. Fungal Genet Biol 43(4):261–272CrossRefGoogle Scholar
  4. An G-H, Johnson EA (1990) Influence of light on growth and pigmentation of the yeast Phaffia rhodozyma. Antonie Leeuwenhoek 57(4):191–203CrossRefGoogle Scholar
  5. An G-H, Schuman DB, Johnson EA (1989) Isolation of Phaffia rhodozyma mutants with increased astaxanthin content. Appl Environ Microbiol 55(1):116–124Google Scholar
  6. An G-H, Bielich J, Auerbach R, Johnson EA (1991) Isolation and characterization of carotenoid hyperproducing mutants of yeast by flow cytometry and cell sorting. Biotechnol NY 9(1):70–73CrossRefGoogle Scholar
  7. An G-H, Kim C-H, Choi E-S, Rhee S-K (1996) Medium optimization for cultivation of carotenoid hyperproducing Phaffia rhodozyma mutant HT-5FO1C. J Ferment Bioeng 82(5):515–518CrossRefGoogle Scholar
  8. An G-H, Jang BG, Cho MH (2001) Cultivation of the carotenoid-hyperproducing mutant 2A2N of the red yeast Xanthophyllomyces dendrorhous (Phaffia rhodozyma) with molasses. J Biosci Bioeng 92(2):121–125CrossRefGoogle Scholar
  9. Andrewes AG, Starr MP (1976) (3R,3′R)-Astaxanthin from the yeast Phaffia rhodozyma. Phytochemistry 15(6):1009–1011CrossRefGoogle Scholar
  10. Andrewes A, Phaff H, Starr M (1976) Carotenoids of Phaffia rhodozyma, a red-pigmented fermenting yeast. Phytochemistry 15(6):1003–1007CrossRefGoogle Scholar
  11. BCC Research (2008) The global market for carotenoids (FOD025C). Accessed 10 July 2010
  12. BCC Research (2009) World markets for fermentation ingredients (FOD020C). Accessed 10 July 2010
  13. Bernhard K, Müller RK, Spruijtenburg R (1984) Process for the preparation of astaxanthin and intermediates in the astaxanthin synthesis. European Patent EP0101597Google Scholar
  14. Berry A, Janssens D, Humbelin M, Jore JP, Hoste B, Cleenwerck I, Vancanneyt M, Bretzel W, Mayer AF, Lopez-Ulibarri R, Shanmugam B, Swings J, Pasamontes L (2003) Paracoccus zeaxanthinifaciens sp. nov., a zeaxanthin-producing bacterium. Int J Syst Evol Microbiol 53(Pt 1):231–238CrossRefGoogle Scholar
  15. Bhosale P, Bernstein PS (2005) Microbial xanthophylls. Appl Microbiol Biotechnol 68(4):445–455CrossRefGoogle Scholar
  16. Breuer M, Ernst H, Hauer B (2008) Method for the production of (4S)-4-hydroxy-3-methoxy-2,6,6-trimethyl-cyclohex-2-enon and derivatives thereof. International Patent WO2008055988Google Scholar
  17. Calo P, Miguel T, Velázquez JB, Villa TG (1995) Mevalonic acid increases trans-astaxanthin and carotenoid biosynthesis in Phaffia rhodozyma. Biotechnol Lett 17(6):575–578CrossRefGoogle Scholar
  18. Cannizzaro C, Rhiel M, Marison I, von Stockar U (2003) On-line monitoring of Phaffia rhodozyma fed-batch process with in situ dispersive Raman spectroscopy. Biotechnol Bioeng 83(6):668–680CrossRefGoogle Scholar
  19. Cannizzaro C, Christensen B, Nielsen J, von Stockar U (2004) Metabolic network analysis on Phaffia rhodozyma yeast using 13C-labeled glucose and gas chromatography–mass spectrometry. Metab Eng 6(4):340–351CrossRefGoogle Scholar
  20. Chan HY, Ho KP (1999) Growth and carotenoid production by pH-stat cultures of Phaffia rhodozyma. Biotechnol Lett 21(11):953–958CrossRefGoogle Scholar
  21. Chumpolkulwong N, Kakizono T, Nagai S, Nishio N (1997) Increased astaxanthin production by Phaffia rhodozyma mutants isolated as resistant to diphenylamine. J Ferment Bioeng 83(5):429–434CrossRefGoogle Scholar
  22. Chun SB, Chin JE, Bai S, An G-H (1992) Strain improvement of Phaffia rhodozyma by protoplast fusion. FEMS Microbiol Lett 93(3):221–226CrossRefGoogle Scholar
  23. Cruz JM, Parajo JC (1998) Improved astaxanthin production by Xanthophyllomyces dendrorhous growing on enzymatic wood hydrolysates containing glucose and cellobiose. Food Chem 63(4):479–484CrossRefGoogle Scholar
  24. Cunningham FX Jr, Gantt E (2005) A study in scarlet: enzymes of ketocarotenoid biosynthesis in the flowers of Adonis aestivalis. Plant J 41(3):478–492CrossRefGoogle Scholar
  25. de la Fuente JL, Peiro E, Diez B, Marcos AT, Schleissner C, Rodriguez Saiz M, Rodriguez Otero C, Cabri W, Barredo JL (2005) Method of production of astaxanthin by fermenting selected strains of Xanthophyllomyces dendrorhous. United States Patent US20050124032A1Google Scholar
  26. de la Fuente JL, Rodríguez-Sáiz M, Schleissner C, Díez B, Peiro E, Barredo JL (2010) High-titer production of astaxanthin by the semi-industrial fermentation of Xanthophyllomyces dendrorhous. J Biotechnol 148(2–3):144–146CrossRefGoogle Scholar
  27. Domínguez-Bocanegra A, Ponce-Noyola T, Torres-Muñoz J (2007) Astaxanthin production by Phaffia rhodozyma and Haematococcus pluvialis: a comparative study. Appl Microbiol Biotechnol 75(4):783–791CrossRefGoogle Scholar
  28. Dong QL, Zhao XM, Ma HW, Xing XY, Sun NX (2006) Metabolic flux analysis of the two astaxanthin-producing microorganisms Haematococcus pluvialis and Phaffia rhodozyma in the pure and mixed cultures. Biotechnol J 1(11):1283–1292CrossRefGoogle Scholar
  29. Ducrey Santopietro LM, Kula MR (1998) Studies of astaxanthin biosynthesis in Xanthophyllomyces dendrorhous (Phaffia rhodozyma). Effect of inhibitors and low temperature. Yeast 14(11):1007–1016CrossRefGoogle Scholar
  30. Echavarri-Erasun C, Johnson EA (2004) Stimulation of astaxanthin formation in the yeast Xanthophyllomyces dendrorhous by the fungus Epicoccum nigrum. FEMS Yeast Res 4(4–5):511–519CrossRefGoogle Scholar
  31. European Food Safety Authority (EFSA) (2010) Scientific opinion on modification of the terms of authorisation of a red carotenoid-rich bacterium Paracoccus carotinifaciens (Panaferd-AX) as feed additive for salmon and trout. EFSA Journal 8(1):1428–1436Google Scholar
  32. Fang TJ, Cheng Y-S (1993) Improvement of astaxanthin production by Phaffia rhodozyma through mutation and optimization of culture conditions. J Ferment Bioeng 75(6):466–469CrossRefGoogle Scholar
  33. Florêncio JA, Soccol CR, Furlanetto LF, Bonfim TMB, Krieger N, Baron M, Fontana JD (1998) A factorial approach for a sugarcane juice-based low cost culture medium: increasing the astaxanthin production by the red yeast Phaffia rhodozyma. Bioprocess Biosyst Eng 19(3):161–164Google Scholar
  34. Flores-Cotera LB, Sánchez S (2001) Copper but not iron limitation increases astaxanthin production by Phaffia rhodozyma in a chemically defined medium. Biotechnol Lett 23(10):793–797CrossRefGoogle Scholar
  35. Flores-Cotera LB, Martin R, Sanchez S (2001) Citrate, a possible precursor of astaxanthin in Phaffia rhodozyma: influence of varying levels of ammonium, phosphate and citrate in a chemically defined medium. Appl Microbiol Biotechnol 55(3):341–347CrossRefGoogle Scholar
  36. Foss P, Renstrøm B, Liaaen-Jensen S (1987) Natural occurrence of enantiomeric and meso astaxanthin 7*-crustaceans including zooplankton. Comp Biochem Physiol B Biochem Mol Biol 86(2):313–314CrossRefGoogle Scholar
  37. Frengova GI, Beshkova DM (2009) Carotenoids from Rhodotorula and Phaffia: yeasts of biotechnological importance. J Ind Microbiol Biotechnol 36(2):163–180CrossRefGoogle Scholar
  38. Frucht LE, Kanon S (2005) Israel grows red algae in the dessert to fight disease. Israel21c. Accessed 9 July 2010
  39. Gerjets T, Sandmann G (2006) Ketocarotenoid formation in transgenic potato. J Exp Bot 57(14):3639–3645CrossRefGoogle Scholar
  40. Girard P, Falconnier B, Bricout J, Vladescu B (1994) β-Carotene producing mutants of Phaffia rhodozyma. Appl Microbiol Biotechnol 41(2):183–191CrossRefGoogle Scholar
  41. Golubev W (1995) Perfect state of Rhodomyces dendrorhous (Phaffia rhodozyma). Yeast 11(2):101–110CrossRefGoogle Scholar
  42. Grung M, D’Souza FML, Borowitzka M, Liaaen-Jensen S (1992) Algal carotenoids 51. Secondary carotenoids 2. Haematococcus pluvialis aplanospores as a source of (3S,3′S)-astaxanthin esters. J Appl Phycol 4(2):165–171CrossRefGoogle Scholar
  43. Gu WL, An GH, Johnson EA (1997) Ethanol increases carotenoid production in Phaffia rhodozyma. J Ind Microbiol Biotechnol 19(2):114–117CrossRefGoogle Scholar
  44. Guerin M, Huntley ME, Olaizola M (2003) Haematococcus astaxanthin: applications for human health and nutrition. Trends Biotechnol 21(5):210–216CrossRefGoogle Scholar
  45. Harker M, Hirschberg J, Oren A (1998) Paracoccus marcusii sp. nov., an orange Gram-negative coccus. Int J Syst Bacteriol 48:543–548Google Scholar
  46. Hasunuma T, Miyazawa S, Yoshimura S, Shinzaki Y, Tomizawa K, Shindo K, Choi SK, Misawa N, Miyake C (2008) Biosynthesis of astaxanthin in tobacco leaves by transplastomic engineering. Plant J 55(5):857–868CrossRefGoogle Scholar
  47. Hazen T (1899) The life history of Sphaerella lacustris. Mem Torrey Bot Club 6(3):211–247Google Scholar
  48. Hermosilla G, Martinez C, Retamales P, Leon R, Cifuentes V (2003) Genetic determination of ploidy level in Xanthophyllomyces dendrorhous. Antonie Leeuwenhoek 84(4):279–287CrossRefGoogle Scholar
  49. Higuera-Ciapara I, Felix-Valenzuela L, Goycoolea FM (2006) Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr 46(2):185–196CrossRefGoogle Scholar
  50. Ho KP, Tam CY, Zhou B (1999) Growth and carotenoid production of Phaffia rhodozyma in fed-batch cultures with different feeding methods. Biotechnol Lett 21(2):175–178CrossRefGoogle Scholar
  51. Hoshino T, Ojima K, Setoguchi Y (1999) DNA sequences encoding enzymes involved in production of isoprenoids. European Patent EP0955363A2Google Scholar
  52. Hoshino T, Ojima K, Setoguchi Y (2000) Astaxanthin synthase. European Patent EP1035206A3Google Scholar
  53. Hoshino T, Setoguchi Y, Takagi Y (2008) Astaxanthin production using fed-batch process by Phaffia rhodozyma. United States Patent US7432076B2Google Scholar
  54. Hu Z-C, Zheng Y-G, Wang Z, Shen Y-C (2005) Effect of sugar-feeding strategies on astaxanthin production by Xanthophyllomyces dendrorhous. World J Microbiol Biotechnol 21(5):771–775CrossRefGoogle Scholar
  55. Hu Z-C, Zheng Y-G, Wang Z, Shen Y-C (2006) pH control strategy in astaxanthin fermentation bioprocess by Xanthophyllomyces dendrorhous. Enzyme Microb Technol 39(4):586–590CrossRefGoogle Scholar
  56. Hu Z-C, Zheng YG, Wang Z, Shen YC (2007) Production of astaxanthin by Xanthophyllomyces dendrorhous ZJUT46 with fed-batch fermentation in 2.0 M3 fermentor. Food Technol Biotechnol 45(2):209–212Google Scholar
  57. Hussein G, Sankawa U, Goto H, Matsumoto K, Watanabe H (2006) Astaxanthin, a carotenoid with potential in human health and nutrition. J Nat Prod 69(3):443–449CrossRefGoogle Scholar
  58. Jacobson GK, Jolly SO, Sedmak JJ, Skatrud TJ, Wasileski JM (1999) Astaxanthin over-producing strains of Phaffia rhodozyma, methods for their cultivation, and their use in animal feeds. United States Patent US6015684Google Scholar
  59. Jayaraj J, Devlin R, Punja Z (2008) Metabolic engineering of novel ketocarotenoid production in carrot plants. Transgenic Res 17(4):489–501CrossRefGoogle Scholar
  60. Johnson EA, An G-H (1991) Astaxanthin from microbial sources. Crit Rev Biotechnol 11(4):297–326CrossRefGoogle Scholar
  61. Johnson EA, Lewis MJ (1979) Astaxanthin formation by the yeast Phaffia rhodozyma. J Gen Microbiol 115(1):173–183Google Scholar
  62. Johnson EA, Schroeder A (1996) Biotechnology of astaxanthin production in Phaffia rhodozyma. In: Takeoka GR, Teranishi R, Williams PJ, Kobayashi A (eds) Biotechnology for improved foods and flavors. ACS Symposium, Series 637, American Chemical Society, Washington, DC, pp 39–50Google Scholar
  63. Kajiwara S, Fraser PD, Kondo K, Misawa N (1997) Expression of an exogenous isopentenyl diphosphate isomerase gene enhances isoprenoid biosynthesis in Escherichia coli. Biochem J 324(Pt 2):421–426Google Scholar
  64. Kato F, Hino T, Nakaji A, Tanaka M, Koyama Y (1995) Carotenoid synthesis in Streptomyces setonii ISP5395 is induced by the gene crtS, whose product is similar to a sigma factor. Mol Gen Genet 247(3):387–390CrossRefGoogle Scholar
  65. Kesava SS, An G-H, Kim C-H, Rhee S-K, Choi E-S (1998) An industrial medium for improved production of carotenoids from a mutant strain of Phaffia rhodozyma. Bioprocess Biosyst Eng 19(3):165–170Google Scholar
  66. Kim S-J, Kim G-J, Park D-H, Ryu Y-W (2003) High-level production of astaxanthin by fed-batch culture of mutant strain Phaffia rhodozyma AJ-6-1. J Microbiol Biotechnol 13(2):175–181Google Scholar
  67. Kim JH, Kang SW, Kim SW, Chang HI (2005) High-level production of astaxanthin by Xanthophyllomyces dendrorhous mutant JH1 using statistical experimental designs. Biosci Biotechnol Biochem 69(9):1743–1748CrossRefGoogle Scholar
  68. Kim SK, Lee JH, Lee CH, Yoon YC (2007) Increased carotenoid production in Xanthophyllomyces dendrorhous G276 using plant extracts. J Microbiol 45(2):128–132Google Scholar
  69. Kitahara T (1984) Carotenoids in the Pacific salmon during the marine period. Comp Biochem Physiol B Biochem Mol Bio 78(4):859–862CrossRefGoogle Scholar
  70. Kusdiyantini E, Gaudin P, Goma G, Blanc PJ (1998) Growth kinetics and astaxanthin production of Phaffia rhodozyma on glycerol as a carbon source during batch fermentation. Biotechnol Lett 20(10):929–934CrossRefGoogle Scholar
  71. Lee JH, Kim YT (2006) Cloning and characterization of the astaxanthin biosynthesis gene cluster from the marine bacterium Paracoccus haeundaensis. Gene 370:86–95CrossRefGoogle Scholar
  72. Lewis MJ, Ragot N, Berlant MC, Miranda M (1990) Selection of astaxanthin-overproducing mutants of Phaffia rhodozyma with beta-ionone. Appl Environ Microbiol 56(9):2944–2945Google Scholar
  73. Liu YS, Wu JY (2006) Use of n-hexadecane as an oxygen vector to improve Phaffia rhodozyma growth and carotenoid production in shake-flask cultures. J Appl Microbiol 101(5):1033–1038CrossRefGoogle Scholar
  74. Liu YS, Wu JY (2007a) Optimization of cell growth and carotenoid production of Xanthophyllomyces dendrorhous through statistical experiment design. Biochem Eng J 36(2):182–189CrossRefGoogle Scholar
  75. Liu YS, Wu JY (2007b) Perfusion culture process plus H2O2 stimulation for efficient astaxanthin production by Xanthophyllomyces dendrorhous. Biotechnol Bioeng 97(3):568–573CrossRefGoogle Scholar
  76. Liu YS, Wu JY (2008) Modeling of Xanthophyllomyces dendrorhous growth on glucose and overflow metabolism in batch and fed-batch cultures for astaxanthin production. Biotechnol Bioeng 101(5):996–1004CrossRefGoogle Scholar
  77. Liu YS, Wu JY, Ho KP (2006) Characterization of oxygen transfer conditions and their effects on Phaffia rhodozyma growth and carotenoid production in shake-flask cultures. Biochem Eng J 27(3):331–335CrossRefGoogle Scholar
  78. Liu ZQ, Zhang JF, Zheng YG, Shen YC (2008) Improvement of astaxanthin production by a newly isolated Phaffia rhodozyma mutant with low-energy ion beam implantation. J Appl Microbiol 104(3):861–872CrossRefGoogle Scholar
  79. Lorenz R, Cysewski G (2000) Commercial potential for Haematococcus microalgae as a natural source of astaxanthin. Trends Biotechnol 18(4):160–167CrossRefGoogle Scholar
  80. Mann V, Harker M, Pecker I, Hirschberg J (2000) Metabolic engineering of astaxanthin production in tobacco flowers. Nat Biotechnol 18:888–892CrossRefGoogle Scholar
  81. Margalith PZ (1999) Production of ketocarotenoids by microalgae. Appl Microbiol Biotechnol 51(4):431–438CrossRefGoogle Scholar
  82. Martín JF, Gudina E, Barredo JL (2008) Conversion of beta-carotene into astaxanthin: two separate enzymes or a bifunctional hydroxylase–ketolase protein? Microb Cell Fact 7:3CrossRefGoogle Scholar
  83. Masamoto K, Misawa N, Kaneko T, Kikuno R, Toh H (1998) ß-Carotene hydroxylase gene from the cyanobacterium Synechocystis sp. PCC6803. Plant Cell Physiol 39(5):560–564Google Scholar
  84. Matsuno T (2001) Aquatic animal carotenoids. Fish Sci 67(5):771–783CrossRefGoogle Scholar
  85. Meyer PS, du Preez JC (1993) Effect of acetic acid on astaxanthin production by Phaffia rhodozyma. Biotechnol Lett 15(9):919–924CrossRefGoogle Scholar
  86. Meyer PS, du Preez JC (1994a) Astaxanthin production by a Phaffia rhodozyma mutant on grape juice. World J Microbiol Biotechnol 10(2):178–183CrossRefGoogle Scholar
  87. Meyer PS, du Preez JC (1994b) Effect of culture conditions on astaxanthin production by a mutant of Phaffia rhodozyma in batch and chemostat culture. Appl Biochem Biotechnol 40(6):780–785Google Scholar
  88. Meyer PS, du Preez JC, Kilian SG (1993) Selection and evaluation of astaxanthin-overproducing mutants of Phaffia rhodozyma. World J Microbiol Biotechnol 9:514–520CrossRefGoogle Scholar
  89. Meyer PS, du Preez JC, van Dyk MS (1994) The effect of monoterpenes on astaxanthin production by a mutant of Phaffia rhodozyma. Biotechnol Lett 16(2):125–128CrossRefGoogle Scholar
  90. Miki W (1991) Biological functions and activities of animal carotenoids. Pure Appl Chem 63(1):141–146CrossRefGoogle Scholar
  91. Miller M, Yoneyama M, Soneda M (1976) Phaffia, a new yeast genus in the Deuteromycotina (Blastomycetes). Int J Syst Bacteriol 26(2):286–291CrossRefGoogle Scholar
  92. Miura Y, Kondo K, Saito T, Shimada H, Fraser PD, Misawa N (1998a) Production of the carotenoids lycopene, beta-carotene, and astaxanthin in the food yeast Candida utilis. Appl Environ Microbiol 64(4):1226–1229Google Scholar
  93. Miura Y, Kondo K, Shimada H, Saito T, Nakamura K, Misawa N (1998b) Production of lycopene by the food yeast, Candida utilis that does not naturally synthesize carotenoid. Biotechnol Bioeng 58(2–3):306–308CrossRefGoogle Scholar
  94. Moriel DG, Chociai MB, Machado IMP, Fontana JD, Bonfim TMB (2005) Effect of feeding methods on the astaxanthin production by Phaffia rhodozyma in fed-batch process. Braz Arch Biol Technol 48(3):397–401CrossRefGoogle Scholar
  95. Morris WL, Ducreux LJ, Fraser PD, Millam S, Taylor MA (2006) Engineering ketocarotenoid biosynthesis in potato tubers. Metab Eng 8(3):253–263CrossRefGoogle Scholar
  96. Nakajima Y, Inokuchi Y, Shimatawa M, Otsubo K, Ishibashi T, Hara H (2008) Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivo. J Pharm Pharmacol 60(10):1365–1374CrossRefGoogle Scholar
  97. Naturxan (2010) Accessed 23 August 2010
  98. Ni H, Chen QH, Ruan H, Yang YF, Li LJ, Wu GB, Hu Y, He GQ (2007) Studies on optimization of nitrogen sources for astaxanthin production by Phaffia rhodozyma. J Zhejiang Univ Sci B 8(5):365–370CrossRefGoogle Scholar
  99. Niklitschek M, Alcaino J, Barahona S, Sepulveda D, Lozano C, Carmona M, Marcoleta A, Martinez C, Lodato P, Baeza M, Cifuentes V (2008) Genomic organization of the structural genes controlling the astaxanthin biosynthesis pathway of Xanthophyllomyces dendrorhous. Biol Res 41(1):93–108CrossRefGoogle Scholar
  100. Ojima K, Breitenbach J, Visser H, Setoguchi Y, Tabata K, Hoshino T, van den Berg J, Sandmann G (2006) Cloning of the astaxanthin synthase gene from Xanthophyllomyces dendrorhous (Phaffia rhodozyma) and its assignment as a beta-carotene 3-hydroxylase/4-ketolase. Mol Genet Genomics 275(2):148–158CrossRefGoogle Scholar
  101. Okagbue RN, Lewis MJ (1984) Use of alfalfa residual juice as a substrate for propagation of the red yeast Phaffia rhodozyma. Appl Microbiol Biotechnol 20(1):33–39CrossRefGoogle Scholar
  102. Palágyi Z, Ferenczy L, Vágvölgyi C (2001) Carbon-source assimilation pattern of the astaxanthin-producing yeast Phaffia rhodozyma. World J Microbiol Biotechnol 17(1):95–97CrossRefGoogle Scholar
  103. Parajo JC, Santos VV, Vazquez M (1998) Production of carotenoids by Phaffia rhodozyma growing on media made from hemicellulosic hydrolysates of Eucalyptus globulus wood. Biotechnol Bioeng 59(4):501–506CrossRefGoogle Scholar
  104. Peng F, Li A (2008) Optimization of carotenoid fermentation medium of Phaffia rhodozyma by BP neural network and genetic algorithm. Ying Yong Yu Huan Jing Sheng Wu Xue Bao 14(6):834–837Google Scholar
  105. Phaff H, Miller M, Yoneyama M, Soneda M (1972) A comparative study of the yeast florae associated with trees on the Japanese islands and in the west coast of North America. In: Gyozo T (ed) Fourth International Fermentation Symposium proceedings: fermentation technology today. Society of Fermentation Technology, Osaka, pp 759–774Google Scholar
  106. Ramírez J, Gutierrez H, Gschaedler A (2001) Optimization of astaxanthin production by Phaffia rhodozyma through factorial design and response surface methodology. J Biotechnol 88(3):259–268CrossRefGoogle Scholar
  107. Ramírez J, Obledo N, Arellano M, Herrera E (2006) Astaxanthin production by Phaffia rhodozyma in a fed-batch culture using a low cost medium feeding. eGnosis 4:1–9Google Scholar
  108. Rayton S, Rayton J, Foley L, Jones PW (2006) Ketocarotenoids from Adonis palaestina. International Patent WO2006119346Google Scholar
  109. Reynders MB, Rawlings DE, Harrison STL (1996) Studies on the growth, modelling and pigment production by the yeast Phaffia rhodozyma during fed-batch cultivation. Biotechnol Lett 18(6):649–654CrossRefGoogle Scholar
  110. Reynders MB, Rawlings DE, Harrison STL (1997) Demonstration of the Crabtree effect in Phaffia rhodozyma during continuous and fed-batch cultivation. Biotechnol Lett 19(6):549–552CrossRefGoogle Scholar
  111. Rodriguez-Saiz M, Godio RP, Alvarez V, de la Fuente JL, Martin JF, Barredo JL (2009) The NADP-dependent glutamate dehydrogenase gene from the astaxanthin producer Xanthophyllomyces dendrorhous: use of its promoter for controlled gene expression. Mol Biotechnol 41(2):165–172CrossRefGoogle Scholar
  112. Rodriguez-Saiz M, de la Fuente JL, Barredo JL (2010) Xanthophyllomyces dendrorhous for the industrial production of astaxanthin. Appl Microbiol Biotechnol. doi:10.1007/s00253-010-2814-x, Epub ahead of printGoogle Scholar
  113. Rüttimann A (1999) Dienolether condensations—a powerful tool in carotenoid synthesis. Pure Appl Chem 71(12):2285–2293CrossRefGoogle Scholar
  114. Sandmann G, Misawa N (2002) Fungal carotenoids. In: Osiewacz HD (ed) The Mycota X; industrial application. Springer, Berlin, pp 247–262Google Scholar
  115. Sauer GM, Flachmann R, Schopfer CR, Leps M, Bridg-Giannakopoulos H (2008a) New ketolases for the production of ketokarotenoids in Tagetes. International Patent WO2008058946Google Scholar
  116. Sauer GM, Flachmann R, Schopfer CR, Leps M, Bridg-Giannakopoulos H, Winner B, Eisenreich R (2008b) Plastid–lipid-associated protein promoters for the production of ketokarotenoids in Tagetes. International Patent WO2008058948Google Scholar
  117. Schloemer GC, Davis JL (2001) Preparation of astaxanthin. International Patent WO0181301Google Scholar
  118. Schmidhauser TJ, Lauter FR, Schumacher M, Zhou W, Russo VE, Yanofsky C (1994) Characterization of al-2, the phytoene synthase gene of Neurospora crassa. Cloning, sequence analysis, and photoregulation. J Biol Chem 269(16):12060–12066Google Scholar
  119. Schroeder WA, Johnson EA (1993) Antioxidant role of carotenoids in Phaffia rhodozyma. J Gen Microbiol 139(5):907–912Google Scholar
  120. Schroeder WA, Johnson EA (1995a) Carotenoids protect Phaffia rhodozyma against singlet oxygen damage. J Ind Microbiol Biotechnol 14(6):502–507Google Scholar
  121. Schroeder WA, Johnson EA (1995b) Singlet oxygen and peroxyl radicals regulate carotenoid biosynthesis in Phaffia rhodozyma. J Biol Chem 270(31):18374–18379CrossRefGoogle Scholar
  122. Seybold A, Goodwin TW (1959) Occurrence of astaxanthin in the flower petals of Adonis annua L. Nature 184(Suppl 22):1714–1715CrossRefGoogle Scholar
  123. Sharpe PL, Ye RW, Zhu QQ (2008) Carotenoid production in a recombinant oleaginous yeast. International Patent WO2008073367Google Scholar
  124. Shimada H, Kondo K, Fraser PD, Miura Y, Saito T, Misawa N (1998) Increased carotenoid production by the food yeast Candida utilis through metabolic engineering of the isoprenoid pathway. Appl Environ Microbiol 64(7):2676–2680Google Scholar
  125. Steinbrenner J, Sandmann G (2006) Transformation of the green alga Haematococcus pluvialis with a phytoene desaturase for accelerated astaxanthin biosynthesis. Appl Environ Microbiol 72(12):7477–7484CrossRefGoogle Scholar
  126. Sun N, Lee S, Song KB (2004) Characterization of a carotenoid-hyperproducing yeast mutant isolated by low-dose gamma irradiation. Int J Food Microbiol 94(3):263–267CrossRefGoogle Scholar
  127. Tischer J (1944) Über die Carotinoide von Hämatococcus pluvialis. III. (Carotinoide der Süßwasseralgen. IX. Teil). Hoppe Seylers Z Physiol Chem 281(5–6):143–155Google Scholar
  128. Trueheart J, Bailey RB, Doten R, Madden KT, Mayorga M, Dueppen D, Dunn JG (2009) Production of carotenoids in oleaginous yeast and fungi. International Patent WO2009126890Google Scholar
  129. Tsubokura A, Yoneda H, Mizuta H (1999) Paracoccus carotinifaciens sp. nov., a new aerobic Gram-negative astaxanthin-producing bacterium. Int J Syst Bacteriol 49:277–282CrossRefGoogle Scholar
  130. Turujman SA, Wamer WG, Wei RR, Albert RH (1997) Rapid liquid chromatographic method to distinguish wild salmon from aquacultured salmon fed synthetic astaxanthin. J AOAC Int 80(3):622–632Google Scholar
  131. Ukibe K, Hashida K, Yoshida N, Takagi H (2009) Metabolic engineering of Saccharomyces cerevisiae for astaxanthin production and oxidative stress tolerance. Appl Environ Microbiol 75(22):7205–7211CrossRefGoogle Scholar
  132. van den Brink HM, van Gorcom RFM, van den Hondel CAMJJ, Punt PJ (1998) Cytochrome P450 enzyme systems in fungi. Fungal Genet Biol 23(1):1–17CrossRefGoogle Scholar
  133. Vázquez M (2001) Effect of the light on carotenoid profiles of Xanthophyllomyces dendrorhous strains (formerly Phaffia rhodozyma). Food Technol Biotechnol 39(2):123–128Google Scholar
  134. Vázquez M, Martin AM (1998) Optimization of Phaffia rhodozyma continuous culture through response surface methodology. Biotechnol Bioeng 57(3):314–320CrossRefGoogle Scholar
  135. Vázquez M, Santos V (1998) 3-Hydroxy-3′, 4′-didehydro-beta-psi-caroten-4-one (HDCO) from Xanthophyllomyces dendrorhous (Phaffia rhodozyma) cultivated on xylose media. Biotechnol Lett 20(2):181–182CrossRefGoogle Scholar
  136. Verdoes JC, Krubasik KP, Sandmann G, van Ooyen AJ (1999a) Isolation and functional characterisation of a novel type of carotenoid biosynthetic gene from Xanthophyllomyces dendrorhous. Mol Gen Genet 262(3):453–461CrossRefGoogle Scholar
  137. Verdoes JC, Misawa N, van Ooyen AJJ (1999b) Cloning and characterization of the astaxanthin biosynthetic gene encoding phytoene desaturase of Xanthophyllomyces dendrorhous. Biotechnol Bioeng 63(6):750–755CrossRefGoogle Scholar
  138. Verdoes JC, Sandmann G, Visser H, Diaz M, van Mossel M, van Ooyen AJ (2003) Metabolic engineering of the carotenoid biosynthetic pathway in the yeast Xanthophyllomyces dendrorhous (Phaffia rhodozyma). Appl Environ Microbiol 69(7):3728–3738CrossRefGoogle Scholar
  139. Verwaal R, Wang J, Meijnen JP, Visser H, Sandmann G, van den Berg JA, van Ooyen AJ (2007) High-level production of beta-carotene in Saccharomyces cerevisiae by successive transformation with carotenogenic genes from Xanthophyllomyces dendrorhous. Appl Environ Microbiol 73(13):4342–4350CrossRefGoogle Scholar
  140. Visser H, van Ooyen AJ, Verdoes JC (2003) Metabolic engineering of the astaxanthin-biosynthetic pathway of Xanthophyllomyces dendrorhous. FEMS Yeast Res 4(3):221–231CrossRefGoogle Scholar
  141. Visser H, Sandmann G, Verdoes JC (2005) Xanthophylls in fungi: metabolic engineering of the astaxanthin biosynthetic pathway in Xantophyllomyces dendrorhous. Methods in biotechnology: microbial processes and products. Humana, TotowaGoogle Scholar
  142. Wang W, Yu L (2009) Effects of oxygen supply on growth and carotenoids accumulation by Xanthophyllomyces dendrorhous. Z Naturforsch C 64(11–12):853–858Google Scholar
  143. Wang W, Yu L, Zhou P (2006) Effects of different fungal elicitors on growth, total carotenoids and astaxanthin formation by Xanthophyllomyces dendrorhous. Bioresour Technol 97(1):26–31CrossRefGoogle Scholar
  144. Wery J, Gutker D, Renniers AC, Verdoes JC, Van Ooyen AJ (1997) High copy number integration into the ribosomal DNA of the yeast Phaffia rhodozyma. Gene 184:89–97CrossRefGoogle Scholar
  145. Wery J, Verdoes JC, Van Ooyen AJJ (1998) Efficient transformation of the astaxanthin-producing yeast Phaffia rhodozyma. Biotechnol Tech 12:399–405CrossRefGoogle Scholar
  146. Widmer E, Zell R, Broger EA, Crameri Y, Wagner HP, Dinkel J, Schlageter M, Lukac T (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
  147. Yamane Y, Higashida K, Nakashimada Y, Kakizono T, Nishio N (1997a) Astaxanthin production by Phaffia rhodozyma enhanced in fed-batch culture with glucose and ethanol feeding. Biotechnol Lett 19(11):1109–1111CrossRefGoogle Scholar
  148. Yamane Y, Higashida K, Nakashimada Y, Kakizono T, Nishio N (1997b) Influence of oxygen and glucose on primary metabolism and astaxanthin production by Phaffia rhodozyma in batch and fed-batch cultures: kinetic and stoichiometric analysis. Appl Environ Microbiol 63(11):4471–4478Google Scholar
  149. Yokoyama A, Izumida H, Miki W (1994) Production of astaxanthin and 4-ketozeaxanthin by the marine bacterium, Agrobacterium aurantiacum. Biosci Biotechnol Biochem 58:1842–1844CrossRefGoogle Scholar
  150. Zheng YG, Hu ZC, Wang Z, Shen YC (2006) Large-scale production of astaxanthin by Xanthophyllomyces dendrorhous. Food Bioprod Process 84(2):164–166CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Isabell Schmidt
    • 1
  • Hendrik Schewe
    • 1
  • Sören Gassel
    • 2
  • Chao Jin
    • 2
  • John Buckingham
    • 3
  • Markus Hümbelin
    • 4
  • Gerhard Sandmann
    • 2
  • Jens Schrader
    • 1
  1. 1.Karl-Winnacker-InstitutFrankfurtGermany
  2. 2.Institute for Molecular BioscienceGoethe UniversityFrankfurtGermany
  3. 3.DSM Nutritional Products GmbHGrenzach-WyhlenGermany
  4. 4.DSM Nutritional Products LtdKaiseraugstSwitzerland

Personalised recommendations