Structure and Function of the Genes Involved in the Biosynthesis of Carotenoids in the Mucorales

  • Iturriaga, Enrique A. (Area de Genetica, Departamento de Microbiologia y Genetica, Universidad de Salamanca, Edificio Departamental) ;
  • Velayos, Antonio (Area de Genetica, Departamento de Microbiologia y Genetica, Universidad de Salamanca, Edificio Departamental) ;
  • Eslava, Arturo P. (Area de Genetica, Departamento de Microbiologia y Genetica, Universidad de Salamanca, Edificio Departamental)
  • Published : 2000.07.01

Abstract

Carotenoids are widely distributed natural pigments which are in an increasing demand by the market, due to their applicatins in the human food, animal feed, cosmetics, and pharmaceutical industries. Although more than 600 carotenoids have been identified in nature, only a few are industrially important (${\beta}$-carotene, astaxanthin, lutein or lycopene). To date chemical processes manufacture most of the carotenoid production, but the interest for carotenoids of biological origin is growing since theire is an increased public concern over the safety of artificial food colorants. Although much interest and effort has been devoted to the use of biological sources for industrially important carotenoids, only the production of biological ${\beta}$-carotene and astaxanthin has been reported. Among fungi, several Mucorales strains, particularly Blakeslea trispora, have been used to develop fermentation processes for the production of ${\beta}$-carotene on almost competitive cost-price levels. Similarly, the basidiomycetous yeast Xanthophyllomyces dendrorhous (the perfect state of Phaffia rhodozyma), has been proposed as a promising source of astaxanthin. This paper focuses on recent findings on the fungal pathways for carotenoid production, especially the structure and function of the genes involved in the biosynthesis of carotenoids in the Mucorales. An outlook of the possibilities of an increased industrial production of carotenoids, based on metabolic engineering of fungi for carotenoid content and composition, is also discussed.

Keywords

References

  1. Carotenoids, Vols I and II. Britton, G.;S. Liaaen-Jensen;H. P. Pfander
  2. FASEB J. v.9 Introduction. The colourful, fascinating world of the carotenoids: Important physiologic modulators. Olson, J. A.;N. I. Krinsky
  3. J. Nutr. Sci. Vitaminol. v.39 Vitamin A and carotenoids as antioxidants in a physiological context. Olson, J. A.
  4. Annu. Rev. Plant Physiol. Plant Mol. Biol. v.43 Photoprotection and other responses of plants to high light stress. Demmig-Adams, B.;W. W. Adams
  5. Annu. Rev. Plant Physiol. Plant Mol. Biol. v.39 Metabolism and physiology of abscisic acid. Zeevaart, J. A. D.;R. A. Creelman
  6. Molecular actions of carotenoids. Carotenoids in Human Health Olson, J. A.;L. M. Cantfield(ed.);N. I. Krinsky(ed.);J. A. Olson(ed.)
  7. J. Dairy Sci. v.76 Role of carotenoids in the immune response. Chew, B. P.
  8. Cancer Epidemiol. Biomarkers Prev. v.7 An international evaluation of the cancer preventive potential of carotenoids. Vainio, H.;M. Rautalahti
  9. J. Natl. Cancer Inst. v.17 Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. Giovannucci, E.
  10. Am. J. Clin. Nutr. v.63 Bioavailability of a natural isomer mixture compared with synthetic alltrans β-carotene in human serum. Ben-Amotz, A.;Y. Levy
  11. Carotenoids. Isler, O.
  12. Arch. Biochem. Biophys. v.27 Lycopersicon selections containing a high content of carotenes and colorless polyenes. II. The mechanism of carotene biosynthesis. Porter, J. W.;R. E. Lincoln
  13. The Biochemistry of Carotenoids. 2nd ed. Goodwin, T. W.
  14. Carotenoids. Chemistry and Biology Krinsky, N. I.;M. M. Mathews-Roth;R. F. Taylor
  15. Production of carotenoids with fungi. Cerda-Olmedo, E.
  16. Eur. J. Biochem. v.223 Carotenoid biosynthesis in microorganisms and plants. Sandmann, G.
  17. J. Bacteriol. v.176 Eubacteria show their true colors: genetics of carotenoid pigment biosynthesis from microbes to plants. Armstrong, G. A.
  18. FASEB J. v.9 Structure and properties of carotenoids in relation to function. Britton, G.
  19. Annu. Rev. Microbiol. v.51 Genetics of eubacterial carotenoid biosynthesis: a colorful tale. Armstrong, G. A.
  20. Annu. Rev. Plant Physiol. Plant Mol. Biol. v.49 Genes and enzymes of carotenoids biosynthesis in plants. Cunningham, F. X., Jr.;E. Gantt
  21. Biochem. J. v.295 Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate. Rohmer, M.;M. Knani;P. Simonin;B. Sutter;H. Sahm
  22. FEBS Lett. v.400 Biosynthesis of isoprenoids in higher plant chloroplasts proceeds via a mevalonate-independent pathway. Lichtenthaler, H. K.;J. Schwender;A. Disch;M. Rohmer
  23. Biochem. J. v.333 Distribution of the mevalonate and glyceraldehyde phosphate/pyruvate pathways for isoprenoid biosynthesis in unicellular algae and the cyanobacterium Synechocystis PCC 6714. Disch, A.;J. Schwender;C. Muller;H. K. Lichtenthaler;M. Rohmer
  24. FEMS Microbiol. Lett. v.168 On the absence of the glyceraldehyde 3-phosphate/pyruvate pathway for isoprenoid biosynthesis in fungi and yeasts. Disch, A.;M. Rohmer
  25. Yeast v.14 Studies of astaxanthin biosynthesis in Xanthophyllomyces dendrorhous (Phaffia rhodozyma). Effect of inhibitors and low temperature. Ducrey Sanpietro, L. M.;M. R. Kula
  26. Biochim. Biophys. Acta v.1446 Carotenoid hydroxylase from Haematococcus pluvialis: cDNA sequence, regulation and functional complementation. Linden, H.
  27. Biochim. Biophys. Acta v.450 The subcellular distribution of carotenoids in Phycomyces blakesleeanus C115 carS42 mad-107 (-). Riley, G. J. P.;P. M. Bramley
  28. Cytobios v.34 The biosynthesis of carotenes in cell organelles of Phycomyces blake-sleeanus C115 carS42 mad-107 (-). Riley, G. J. P.;P. M. Bramley
  29. Trends Genet. v.8 Sex, light and carotenes: the development of Phycomyces. Corrochano, L. M.;E. Cerda-Olmedo
  30. Biochem. J. v.52 Studies in carotenogenesis. 5. Carotene production by various mutants of Phycomyces blakesleeanus and Phycomyces nitens. Goodwin, T. W.;L. A. Griffits
  31. Plant Physiol v.43 Carotenes and retinal in Phycomyces mutants. Meissner, G.;M. Delbruck
  32. Mol. Gen. Genet. v.121 Complementation between mutants of Phycomyces deficient with respect to carotenogenesis. Ootaki, T.;A. C. Lighty;M. Delbruck;W. J. Hsu
  33. Bot. Gaz. v.139 Genetics of Ustilago violacea. II. Polymorphism of color and nutritional requirements of sporidia from natural popula-tions. Garber, E. D.;M. L. Baird;L. M. Weiss
  34. Carotene. Cerda-Olmedo, E.;E.Cerda-Olmedo(ed.);E. D. Lipson (ed.)
  35. The Blue-Light Syndrome Blue light-induced carotenoid biosynthesis in microorganisms. Rau, W.
  36. Methods Enzymol. v.214 Photoregulated carotenoid biosynthetic genes of Neurospora crassa. Morelli, G.;M. A. Nelson;P. Ballario;G. Macino
  37. Photoregulation of fungal gene expression. Cerda-Olmedo, E.;L. M. Corrochano;R. C. Jennings(ed.);G. Zucchelli(ed.);F. Ghetti(ed.);G. Colombetti(ed.)
  38. Fungal Genet. Biol. v.22 Blue light regulation in Neurospora crassa. Linden, H.;P. Ballario;G. Macino
  39. J. Gen. Microbiol. v.64 Effect of light on beta-carotene accumulation in Blakeslea trispora. Sutter, R. P.
  40. Antonie Van Leeuwenhoek v.57 Influence of light on growth and pigmentation of the yeast Phaffia rhodozyma. An, G. H.;E. A. Johnson
  41. Science v.123 In-creased production of carotene by mixed + and - cultures of Choanephora cucurbitarum. Barnett, H. L.;V. G. Lilly;R. F. Krause
  42. J. Agric. Food Chem. v.6 Microbiological production of beta-carotene in shaken flasks. Anderson, R. F.;M. Arnold;G. E. N. Nelson;A. Ciegler
  43. Mol. Gen. Genet. v.148 Regulation of carotene synthesis in Phycomyces. Murillo, F. J.;E. Cerda-Olmedo
  44. J. Gen. Microbiol. v.132 Sexual activa-tion of carotenogenesis in Phycomyces. Govind, N. S.;E. Cerda-Olmedo
  45. trispora. Science v.168 Trisporic acid synthesis in Blakeslea Sutter, R. P.
  46. Fungal Genet. Biol. v.20 (-) mating type-specific mutants of Phycomyces de-fective in sex pheromone biosynthesis. Sutter, R. P.;A. B. Grandin;B. D. Dye;W. R. Moore
  47. Tetrahedron Lett. v.7 The structure of trisporic-C acid. Caglioti, L.;G. Cainelli;B. Camerino;R. Mondelli;A. Prieto;A. Quilico;T. Salvatori;A. Selva
  48. Eur. J. Biochem. v.48 Regulation of carotene biosynthesis in Phycomyces by vi-tamin-A and beta-ionone. Eslava, A. P.;M. I. Alvarez;E. Cerda-Olmedo
  49. Arch. Microbiol. v.150 End-product regulation of carotenogene-sis in Phycomyces. Bejarano, E. R., F. Parra, F. J. Murillo, and E. Cerda-Olmedo
  50. Phytochem. v.28 Inhibition of phytoene dehydrogenation and activation of caroteno-genesis in Phycomyces. Bejarano, E. R.;E. Cerda-Olmedo
  51. Angew. Botanik v.60 Forderung und Hemmung der Carotin-synthese bei Phycomyces durch Aromaten. Cerda-Olmedo, E.;A. Huttermann
  52. Phytochem. v.25 Chemical modifi-cation of carotenogenesis in Gibberella fujikuroi. Avalos, J.;E. Cerda-Olmedo
  53. Mi-crobiol. Rev. v.46 Chromosomal loci of Neurospora crassa. Perkins, D. D.;A. Radford;D. Newmeyer;M. Bjork-man
  54. Genetics. Eslava, A. P.;E. Cerda-Olmedo(ed.);E. D. Lipson (ed.)
  55. Mol. Gen. Genet. v.102 Segregation of heterokaryons in the asexual cycle of Phycomyces. Heisenberg, M.;E. Cerda-Olmedo
  56. Plant Sci. Lett. v.2 Genetic control of phytoene dehydrogenation in Phycomyces. Eslava, A. P.;E. Cerda-Olmedo
  57. Genet. Res. v.36 Genetics of lycopene cyclization and substrate transfer in beta-carotene biosynthesis in Phycomyces. Torres-Martinez, S.;F. J. Murillo;E. Cerda-Olmedo
  58. Eur. J. Biochem. v.119 Substrate transfer in carotene bio-synthesis in Phycomyces. Murillo, F. J.;S. Torres-Martinez;C. M. Aragon;E. Cerda-Olmedo
  59. Fungal Genet. Biol. v.22 Complementation analysis of carote-nogenic mutants of Mucor circinelloides. Velayos, A.;M. A. Lopez-Matas;M. J. Ruiz-Hidalgo;A. P. Eslava
  60. Planta v.210 Blue-light regulation of phytoene de-hydrogenase (carB) gene expression in Mucor circinelloides. Velayos, A.;J. L. Blasco;M. I. Alvarez;E. A. Iturriaga;A. P. Eslava
  61. Eur. J. Biochem. v.63 An enzyme complex for the dehy-drogenation of phytoene in Phycomyces. Aragon, C. M.;F. J. Murillo;M. D. de la Guardia;E. Cerda-Olmedo
  62. Appl. Environ. Microbiol. v.36 Carotene-superproducing strains of Phy-comyces. Murillo, F. J.;I. L. Calderon;I. Lopez-Diaz;E. Cerda-Olmedo
  63. European Patent Office EP93/00850. Intersexual heterozygous Phycomyces. Cerda-Olmedo, E.;B. J. Mehta;P. van Dijck;B. Koekman
  64. Carslberg Res. Commun. v.49 High fre-quency transformation of Mucor with recombinant plasmid DNA. van Heeswijck, R.;M. I. G. Roncero
  65. Curr. Genet. v.21 Heterologous transfor-mation of Mucor circinelloides with the Phycomyces blakesleeanus leu1 gene. Iturriaga, E. A.;J. M. Diaz-Minguez;E. P. Benito;M. I. Alvarez;A. P. Eslava
  66. Gene v.116 Cloning and sequence analysis of the Mucor circinelloides pyrG gene encoding orotidine-5'-monophosphate decarboxylase: use of pyrG for homologous transformation. Benito, E. P.;J. M. Diaz-Minguez;E. A. Iturriaga;V. Cam-puzano;A. P. Eslava
  67. Mol. Gen. Genet. v.225 Integrative transformation by homologous recombination in the zygomycete Mucor circinelloides. Arnau, J.;L. P. Jepsen;P. Strøman
  68. Curr. Genet. v.23 Gene replacement and ectopic integration in the zygomycete Mucor circinelloides. Arnau, J.;P. Strøman
  69. Mol. Gen. Genet. v.248 Isolation, characteriza-tion and transformation, by autonomous replication, of Mucor circinelloides OMPdecase-deficient mutants. Benito, E. P.;V. Campuzano;M. A. Lopez-Matas;J. I. De Vicente;A. P. Eslava
  70. Curr. Microbiol. v.39 Heterologous expression of the Phycomyces blakesleeanus phytoene dehydrogenase gene (carB) in Mu-cor circinelloides. Ruiz-Hidalgo, M. J.;A. P. Eslava;M. I. Alvarez;E. P. Benito
  71. Bot. Acta v.108 Carotenoid mutants of Mucor circinelloides. Ruiz-Hidalgo, M. J.;M. A. Lopez-Matas;A. Velayos;P. D. Fraser;P. M. Bramley;A. P. Eslava
  72. Exp. Mycol. v.19 Mutants of the carotenoid pathway of Mucor circinelloides. Navarro, E.;G. Sandmann;S. Torres-Martinez
  73. Biochim. Biophys. Acta v.1289 Carote-noid biosynthesis in wild type and mutant strains of Mu-cor circinelloides. Fraser, P. D.;M. J. Ruiz-Hidalgo;M. A. Lopez-Matas;M. I.Alvarez;A. P. Eslava;P. M. Bramley
  74. Fungal Genet. Biol. v.25 Gibberellin biosyn-thetic pathway in Gibberella fujikuroi: evidence for a gene cluster. Tudzynski, B.;K. Holter
  75. Arch. Biochem. Biophys. v.266 Purification of geranylgeranyl diphosphate synthase from Phycomyces blakesleanus. Brinkhaus, F. L.;H. C. Rilling
  76. J. Biol. Chem. v.273 Identification of an FAD superfamily containing protoporphyrinogen oxi-dases, monoamine oxidases, and phytoene desaturase. Expression and characterization of phytoene desaturase of Myxococcus xanthus. Dailey, T. A.;H. A. Dailey
  77. Mol. Gen. Genet. v.262 Isolation and functional characterisation of a novel type of carotenoid biosynthetic gene from Xan-thophyllomyces dendrorhous. Verdoes, J. C.;P. Krubasic;G. Sandmann;A. J. van Ooyen
  78. Mol. Gen. Genet. v.263 A carotenogenig gene cluster from Brevibacterium linens with novel lyco-pene cyclase genes involved in the synthesis of aromatic carotenoids. Krubasic, P.;G. Sandmann
  79. Appl. Microbiol. Biotechnol. v.42 Mutants of carotene production in Blakeslea trispora. Mehta, B. J.;E. Cerda-Olmedo
  80. Biotechnology (N Y) v.9 Isolation and characterization of carotenoid hyper-producing mutants of yeast by flow cytometry and cell sorting. An, G. H.;J. Bielich;R. Auerbach;E. A. Johnson
  81. Appl. Biochem. Biotechnol. v.66 Photosensitization of the yeast Phaffia rhodozyma at a low temperature for screening carotenoid hyperproducing mutants. An, G. H.
  82. Pro-duction of β-carotene by Mucorales. Avalos, J.;B. J. Mehta;E. Cerda-Olmedo;T. G. Villa(ed.);J. Abalde(ed.)
  83. FEBS Lett. v.306 Independ-ence of the carotene and sterol pathways of Phycomyces. Bejarano, E. R.;E. Cerda-Olmedo
  84. Eur. J. Biochem. v.239 Separate compartments for the produc-tion of sterols, carotenoids and gibberellins in Gibberella fujikuroi. Domenech, C. E.;W. Giordano;J. Avalos;E. Cerda-Olmedo
  85. Biochem. J. v.324 Expression of an exogenous isopentenyl diphos-phate isomerase gene enhances isoprenoid biosynthesis in Escherichia coli. Kajiwara, S.;P. D. Fraser;K. Kondo;N. Misawa
  86. Biotechnol. Bioeng. v.62 Engineered isoprenoid pathway enhances astaxanthin production in Escherichia coli. Wang, C. W.;M. K. Oh;J. C. Liao
  87. Mol. Cell. Biol. v.9 Molecular cloning of a Neurospora crassa carotenoid biosynthetic gene (albino-3) regulated by blue light and the products of the white collar genes. Nelson, M. A.;G. Morelli;A. Carattoli;N. Romano;G. Macino
  88. Mol. Cell. Biol. v.10 Cloning, sequence, and photoregulation of al-1, a carotenoid biosynthetic gene of Neurospora crassa. Schmidhauser, T. J.;F. R. Lauter;V. E. Russo;C. Ya-nofsky
  89. J. Biol. Chem. v.269 Characteri-zation of al-2, the phytoene synthase gene of Neurospora crassa. Cloning, sequence analysis, and photoregulation. Schmidhauser, T. J.;F. R. Lauter;M. Schumacher;W. Zhou;V. E. Russo;C. Yanofsky
  90. Mol. Gen. Genet. v.253 The phytoene dehydrogenase gene of Phycomyces: regulation of its expression by blue light and vitamin A. Ruiz-Hidalgo, M. J.;E. P. Benito;G. Sandmann;A. P. Eslava
  91. Mol. Microbiol. v.13 Molecular characterization of upstream regula-tory sequences controlling the photoinduced expression of the albino-3 gene of Neurospora crassa. Carattoli, A.;C. Cogoni;G. Morelli;G. Macino
  92. EMBO J. v.15 White collar-1, a central regulator of blue light responses in Neurospora, is a zinc finger protein. Ballario, P.;P. Vittorioso;A. Magrelli;C. Talora;A. Cabibbo;G. Macino
  93. EMBO J. v.16 White collar 2, a part-ner in blue-light signal transduction, controlling expres-sion of light-regulated genes in Neurospora crassa. Linden, H.;G. Macino
  94. Eur. J. Biochem. v.267 Overexpression of the crgA gene abolishes light requirement for carotenoid biosynthesis in Mucor circi-nelloides. Navarro, E.;V. L. Ruiz-Perez;S. Torres-Martinez
  95. Trends Microbiol. v.5 White collar proteins: PASsing the light signal in Neurospora crassa. Ballario, P.;G. Macino
  96. Adv. Appl. Microbiol. v.7 Microbial carotenogenesis. Ciegler, A.
  97. Carotenoids. Ninet, L.;J. Renaut;H. J. Peppler(ed.);D. Perlman (ed.)
  98. European Patent WO93/20183 Method for producing beta-carotene us-ing a fungal mated culture. Filkenstein, M.;C. C. Huang;G. S. Byng;B. R. Tsau;J. Leach
  99. Mycopathologia v.90 A review of factors affecting biosynthesis of carotenoids by the order Mucorales. Lampila, L. E.;S. E. Wallen;L. B. Bullerman
  100. US Patent 4,318,987. β-carotene producing strains of the fun-gus Phycomyces blakesleeanus. Murillo, F. J.;I. L. Calderon;I. Lopez-Diaz;E. Cerda-Olmedo
  101. West Virginia Univ. Agr. Exper. Sta. The Production of Carotene by Phycomyces blakesleeanus. Lilly, V. G., H. L. Barnett, and R. F. Krause
  102. J. Appl. Bac-teriol. v.59 Influence of mixed culture conditions on yeast-wall hydrolytic activity of Bacillus circulans WL-12 and on the extractability of astaxanthin from the yeast Phaffia rhodozyma. Okagbue, R. N.;M. J. Lewis
  103. J. Bacteriol. v.156 Isolation and biochemical analysis of Mucor bacilli-formis monomorphic mutants. Ruiz-Herrera, J.;A. Ruiz;E. Lopez-Romero
  104. Appl. Microbiol. v.12 Stimulation of carotenogenesis by microbial cells. Ciegler, A.;Z. Pazola;H. H. Hall
  105. Prog. Lipid Res. v.33 Oleaginous fungi: carotene-rich oil from Phycomyces. Cerda-Olmedo, E.;J. Avalos
  106. Folia Microbiol. (Praha) v.37 Oligounsaturated fatty acid production by selected strains of micromyce-tes. Stredanska, S.;J. Sajbidor
  107. Adv. Exp. Med. Biol. v.405 Novel microbial transforma-tions of steroids. Madyastha, K. M.
  108. J. Nat. Prod. v.61 Microbiological transformation of ma-noyl oxide derivatives by Mucor plumbeus. Fraga, B. M.;P. Gonzalez;R. Guillermo;M. G. Her-nandez
  109. FEMS Microbiol. Rev. v.14 Improve-ment of heavy metal biosorption by mycelial dead bio-masses (Rhizopus arrhizus, Mucor miehei and Penicillium chrysogenum): pH control and cationic activation. Fourest, E.;C. Canal;J. C. Roux
  110. Appl. Biochem. Biotechnol. Biosorption of nickel using filamentous fungi. Mogollon, L.;R. Rodriguez;W. Larrota;N. Ramirez;R. Torres
  111. Plant J. v.11 Transgenic rice (Oryza sativa) endosperm expressing daf-fodil (Narcissus pseudonarcissus) phytoene synthase ac-cumulates phytoene, a key intermediate of provitamin A biosynthesis. Burkhardt, P. K., P. Beyer, J. Wunn, A. Kloti, G. A. Arm-strong, M. Schledz, J. von Lintig, and I. Potrykus
  112. J. Biotechnol. v.59 Metabolic engineer-ing for the production of carotenoids in non-caro-tenogenic bacteria and yeasts. Misawa, N.;H. Shimada
  113. Appl. Environ. Microbiol. v.60 Isolation, se-quence, and characterization of the Cercospora nicotianae phytoene dehydrogenase gene. Ehrenshaft, M.;M. E. Daub
  114. Mol. Gen. Genet. v.255 The geranylgeranyl diphosphate synthase gene of Gibberella fujikuroi: isolation and expression. Mende, K.;V. Homann;B. Tudzynski
  115. Biotechnol. Bioeng. v.63 Cloning and characterization of the astaxanthin biosyn-thetic gene encoding phytoene desaturase of Xanthophyl-lomyces dendrorhous. Verdoes, J. C.;N. Misawa;A. J. van Ooyen