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Microbiological production of tocopherols: current state and prospects

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Abstract

Tocopherols are antioxidants that prevent various diseases caused by oxidative stress. Tocochromanols comprise four isoforms of tocopherols and four isoforms of tocotrienols but α-tocopherol is the most abundant and active isoform in human and animal tissues. Tocopherols are used as dietary supplements for human, as food preservatives, in manufacture of cosmetics, and for fortification of animal feed. Only photosynthetic cells are known to accumulate detectable concentrations of tocopherols. Tocopherols can be extracted and purified or concentrated from vegetable oils and other higher plant materials. However, the concentrations in these higher plant materials are very low and there are high proportions of the less-active homologues of tocopherols. Among the many strains of photosynthetic microorganisms known to accumulate tocopherols, Euglena gracilis is promising for commercial production of α-tocopherol. The growth rate and α-tocopherol contents are relatively high and α-tocopherol comprise more than 97% of all the tocopherols accumulated by Euglena gracilis. Although a lot of work has been done to increase the contents and composition of tocopherols in higher plants through genetic and metabolic engineering, work on genetic modification of microorganisms for increased tocopherol accumulation is scarce. Many cultivation systems have been investigated for efficient production of tocopherol by Euglena gracilis. However, those that involve heterotrophic metabolism are more promising. Bubble columns and flat-plate photobioreactors are more suitable for commercial production of tocopherols, than the tubular, internally illuminated, and open-air photobioreactors.

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References

  • Abalde J, Fabregas J, Herrero C (1991) β-carotene, vitamin C, and vitamin E content of the marine microalga Dunaliella tertiolecta cultured with different nitrogen sources. Biores Technol 38:121–125

    CAS  Google Scholar 

  • Borowitzka MA (1999) Commercial production of microalgae: ponds, tanks, tubes and fermenters. J Biotechnol 7:3–15

    Google Scholar 

  • Bravi M, Spinoglio F, Verdone N, Adami M, Aliboni A, D’Andrea A, De Santis A, Ferri D (2007) Improving the extraction of α-tocopherol-enriched oil from grape seeds by supercritical CO2. Optimization of the extraction conditions. J Food Engineering 78:488–493

    CAS  Google Scholar 

  • Brown MR, Mular M, Miller I, Farmer C, Trenerry C (1999) The vitamin content of microalgae used in aquaculture. J Appl Phycol 11:247–255

    CAS  Google Scholar 

  • Cahoon EB, Hall SE, Ripp KG, Ganzke TS, Hitz WD, Coughlan SJ (2003) Metabolic engineering of vitamin E biosynthesis in plants for tocotrienol production and increased antioxidant content. Nat Biotechnol 21:1082–1087

    CAS  PubMed  Google Scholar 

  • Carballo-Cardenas EC, Tuan PM, Janssen M, Wijffels RH (2003) Vitamin E (α-tocopherol) production by the marine microalgae Dunaliella tertiolecta and Tetraselmis suecica in batch cultivation. Biomolecular Eng 20:139–147

    CAS  Google Scholar 

  • Chen F, Johns MR (1996) Heterotrophic growth of Chlamydomonas reinhardtii on acetate in heterotrophic culture. Process Biochem 31:601–604

    CAS  Google Scholar 

  • Chiu A, Kimball AB (2003) Topical vitamins, minerals and botanical ingredients as modulators of environmental and chronological skin damage. Br J Dermatol 149:681–691

    CAS  PubMed  Google Scholar 

  • Donato M, Vilela MH, Bandarra NM (2003) Fatty acids, sterols, α-tocopherol and total carotenoids composition of Diacronema vlkianum. J Food Lipids 10(4):267–276

    CAS  Google Scholar 

  • Durmaz Y (2007) Vitamin E (α-tocopherol) production by the marine microalga Nannochloropsis oculata (Eustigmatophyceae) in nitrogen limitation. Aquaculture 272:717–722

    CAS  Google Scholar 

  • Endo H, Sansawa H, Nakajima K (1977) Studies on Chlorella reguralis, fast growing strain II: Mixotrophic growth in relation to light intensity and acetate concentration. Plant Cell Physiol 18:199–205

    CAS  Google Scholar 

  • Fabregas J, Herrero C (1990) Vitamin content of four marine microalgae. Potential use as source of vitamins in nutrition. J Ind Microbiol Biotech 5:259–264

    CAS  Google Scholar 

  • Fryer MJ (1992) The antioxidant effects of thylakoid vitamin E (α-tocopherol). Plant Cell Environ 15:381–392

    CAS  Google Scholar 

  • Fujita T, Ogbonna JC, Hideo H, Aoyagi H (2008a) Effect of mixed organic substrate on α-tocopherol production by Euglena gracilis in photoheterotrophic culture. Appl Microbiol Biotechnol 79:371–378

    CAS  PubMed  Google Scholar 

  • Fujita T, Ogbonna JC, Hideo H, Aoyagi H (2008b) Effects of reactive oxygen species on α-tocopherol production in mitochondria and chloroplasts of Euglena gracilis. J Appl Phycol doi:https://doi.org/10.1007/s10811-008-9349-x

    Google Scholar 

  • Giasuddin ASM, Diplock AT (1981) The influence of vitamin E in membrane lipids of mouse fibroblasts in culture. Arch Biochem Biophy 210:348–362

    CAS  Google Scholar 

  • Green J (1958) The distribution of tocopherols during the life cycle of some plants. J Sci Food Agric 9:801–812

    CAS  Google Scholar 

  • Green J, Price SA, Gare L (1959) Tocopherols in microorganisms. Nature (London) 184:1339

    CAS  Google Scholar 

  • Hughes PE, Tove SB (1982) Occurrence of α-tocophrolquinone and α-tocopherolquinol in microorganisms. J Bact 151:1397–1402

    CAS  PubMed  PubMed Central  Google Scholar 

  • Izquierdo MS, Fernandez-Palacios H, Tacon AGJ (2001) Effect of broodstock nutrition on reproductive performance of fish. Aquaculture 197:25–42

    Google Scholar 

  • Kamal-Eldin A, Appelqrist LA (1996) The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids 31:671–701

    CAS  PubMed  Google Scholar 

  • King JW, Favati F, Taylor SL (1996) Production of tocopherol concentrates by supercritical fluid extraction and chromatography. Separation Sci Technol 31(13):1843–1848

    CAS  Google Scholar 

  • Kobayashi M, Kakizono T, Yamaguchi K, Nishio N, Nagai S (1992) Growth and astaxanthin formation of Haematococcus pluvialis in heterotrophic and mixotrophic conditions. J Ferment Bioeng 74:17–20

    CAS  Google Scholar 

  • Kruk U, Strzalka K (1995) Occurance and functions of α-tocopherol quinines in plants. J Plant Physiol 145:405–409

    CAS  Google Scholar 

  • Kusmic C, Barsacchi R, Gualtieri P, Passarelli V (1999) Euglena gracilis as source of the antioxidant vitamin E. Effects of culture conditions in the wild strain and in the natural mutant WZSL. J Appl Phycol 10:555–559

    Google Scholar 

  • Lucy JA (1972) Functional and structural aspects of biological membrane: suggested role of vitamin E in control of membrane permeability and stability. Ann NY Acad Sci 203:4–11

    CAS  PubMed  Google Scholar 

  • Marquez FJ, Sasaki K, Kakizono T, Nishio N, Nagai S (1993) Growth characteristics of Spirulina platensis in mixotrophic and heterotrophic conditions. J Ferment Bioeng 76:408–410

    CAS  Google Scholar 

  • McCay PB, King MM (1980) Vitamin E: its role as biologic free radical scavenger and its relationship to the microsomal mixed-function oxidase system. In: Machin LJ (ed) Vitamin E: a comprehensive treatise. Marcel Dekker, New York, pp 289–318

    Google Scholar 

  • Molero-Gomez A, Pereyra-Lopez C, Martinez de la Ossa E (1996) Recovery of grape seed oil by liquid supercritical carbon dioxide extraction: a comparison with conventional solvent extraction. Chem Engr J 61:227–231

    CAS  Google Scholar 

  • Mori K (1985) Photoautotrophic bioreactor using visible solar rays condensed by fresnel lenses and transmitted through optical fibers. Biotechnol Bioeng Symp 15:331–345

    Google Scholar 

  • Ogbonna JC (2003) Photobioreactors. In Fingerman M, Nagabhushanam R (eds) Recent advances in marine biotechnology. Volume 9, Materials and Bio-processing. Science, pp 315–348

  • Ogbonna JC, Tanaka H (1996) Night biomass loss and changes in biochemical composition of cells during light/dark cyclic culture of Chlorella pyrenoidosa. J Ferment Bioeng 82:558–564

    CAS  Google Scholar 

  • Ogbonna JC, Tanaka H (1998) Cyclic autotrophic/heterotrophic cultivation of photosynthetic cells: a method of achieving continuous cell growth under light/dark cycles. Biores Technol 65:65–72

    CAS  Google Scholar 

  • Ogbonna JC, Tanaka H (2000a) Light requirement and photosynthetic cell cultivation—development of processes for efficient light utilization in photobiorectors. J Appl Phycol 12:207–218

    Google Scholar 

  • Ogbonna JC, Tanaka H (2000b) Production of pure photosynthetic cell biomass for environmental bioresnsors. Material Sci Eng C 12:9–15

    Google Scholar 

  • Ogbonna JC, Yada H, Masui H, Tanaka H (1996) A novel internally illuminated stirred tank photobioreactor for large scale cultivation of photosynthetic cells. J Ferment Bioeng 82:549–555

    Google Scholar 

  • Ogbonna JC, Masui H, Tanaka H (1997) Sequential heterotrophic-autotrophic cultivation—an efficient method for producing Chlorella biomass for health food and animal feed. J Appl Phycol 9:359–366

    Google Scholar 

  • Ogbonna JC, Tomiyama S, Tanaka H (1998) Heterotrophic cultivation of Euglena gracilis Z for efficient production of α-tocopherol. J Appl Phycol 10:67–74

    CAS  Google Scholar 

  • Ogbonna JC, Soejima T, Tanaka H (1999a) An integrated solar and artificial light system for internal illumination of photobioreactors. J Biotechnol 70:289–297

    CAS  PubMed  Google Scholar 

  • Ogbonna JC, Tomiyama S, Tanaka H (1999b) Production of α-tocopherol by sequential heterotrophic-photoautotrophic cultivation of Euglena gracilis. J Biotechnol 70:213–221

    CAS  Google Scholar 

  • Ogbonna JC, Soejima T, Ugwu CU, Tanaka H (2001) An integrated system of solar light, artificial light and organic carbon supply for cyclic photoautotrophic-heterotrophic cultivation of photosynthetic cells under day-night cycles. Biotechnol Lett 23:1401–1406

    CAS  Google Scholar 

  • Ogbonna JC, Ichige E, Tanaka H (2002a) Interaction between photoautotrophic and heterotrophic metabolism in photoheterotrophic cultures of Euglena gracilis. Appl Microbiol Biotechnol 58:532–538

    CAS  PubMed  Google Scholar 

  • Ogbonna JC, Ichige E, Tanaka H (2002b) Regulating the ratio of photoautotrophic to heterotrophic metabolic activities in the photoheterotrophic culture of Euglena gracilis and its application to α-tocopherol production. Biotechnol Lett 24:953–958

    CAS  Google Scholar 

  • Powls R, Redfearn ER (1967) The tocopherols of the blue green algae. Biochem J 104:24C–26C

    CAS  Google Scholar 

  • Qi Q, Hao M, Ng W, Slater SC, Baszis SR, Weiss JD, Valentin HE (2005) Application of Synechococcus nirA promoter to establish an inducible expression system for engineering the Synechocystis tocopherol pathway. Appl Environ Microbiol 71(10):5678–5684

    CAS  PubMed  PubMed Central  Google Scholar 

  • Qureshi AA, Bradlow BA, Brace L, Manganello J, Peterson DM, Pearce BC, Wright JJK, Grapor A, Elson CE (1995) Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids 30:1171–1177

    CAS  PubMed  Google Scholar 

  • Rimbach G, Minihane AM, Majewicz J, Fischer A, Pallauf J, Virgli F, Weinberg PD (2002) Regulation of cell signaling by vitamin E. Proc Nutr Soc 61:415–425

    CAS  PubMed  Google Scholar 

  • Rippert P, Scimemi C, Dubald M, Matringe M (2004) Engineering plant shikimate pathway for production of tocoytrienol and improving herbicide resistance. Plant Physiol 134:92–100

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rock CL, Jacob RJ, Bowen PE (1996) Update on the biological characteristics of the antioxidants micronutrients: Vitamin C, Vitamin E, and the carotenoids. J Am Diet Assoc 96:693–702

    CAS  PubMed  Google Scholar 

  • Ruggeri BA, Gray RJH, Watkins TR, Tomlins RI (1985) Effects of low-temperature acclimation and oxygen stress on tocopherol production in Euglena gracilis Z. Appl Environ Microbiol 50(6):1404–1408

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez Miron A, Gomez CA, Camacho FG, Grima EM, Chisti Y (2000) Bubble-column and airlift photobioreactors for algae culture. AICHE J 46:1872–1887

    Google Scholar 

  • Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med 336:1216–1222

    CAS  PubMed  Google Scholar 

  • Shigeoka S, Onishi T, Nakano Y, Kitaoka S (1986) The contents and sub-cellular distribution of tocopherols in Euglena gracilis. Agric Biol Chem 50:1063–1065

    CAS  Google Scholar 

  • Shigeoka S, Ishiko H, Nakano Y, Mitsunaga T (1992) Isolation and properties of γ-tocopherol methyltransferase in Euglena gracilis. Biochim Biophys Acta 1128:220–226

    CAS  PubMed  Google Scholar 

  • Taketomi H, Shoda K, Katsui G (1983) Results of screening test in tocopherols in microbial realm. Vitamins (Japan) 57:133–138

    CAS  Google Scholar 

  • Takeyama H, Kanamaru A, Yoshino Y, Kakuta H, Kawamura Y, Matsunaga T (1997) Production of antioxidant vitamins β-carotene, vitamin C, and vitamin E by two step culture of Euglena gracilis Z. Biotechnol Bioeng 53:185–190

    CAS  PubMed  Google Scholar 

  • Tani Y, Osuka S (1989) α-tocopherol production by an analog-resistant strain of Euglena gracilis Z. Agric Biol Chem 53:2313–2318

    CAS  Google Scholar 

  • Tani Y, Tsumura H (1989) Screening for tocopherol-producing microorganisms and α-tocopherol production by Euglena gracilis Z. Agric Biol Chem 53:305–312

    CAS  Google Scholar 

  • Torzillo G, Carlozzi P, Pushparaj B, Montaini E, Materassi R (1993) A two plane tubular photobioreactor for outdoor culture of Spirulina. Biotechnol Bioeng 42:891–898

    CAS  PubMed  Google Scholar 

  • Threlfall DR, Goodwin TW (1967) Nature, intracellular distribution and formation of terpenoid quinines in Euglena gracilis. Biochem J 103:573–588

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tredici MR, Materassi R (1992) From open ponds to vertical alveolar panels: the Italian experience in the development of reactors for mass cultivation of photoautotrophic microorganisms. J Appl Phycol 4:221–231

    Google Scholar 

  • Ugwu CU, Ogbonna JC, Tanaka H (2002) Improvement of mass transfer characteristics and productivities of inclined tubular photobioreactors by installation of internal static mixers. Appl Microbiol Biotechnol 58:600–607

    CAS  PubMed  Google Scholar 

  • Valentin HE, Qi Q (2005) Biotechnological production and application of vitamin E: current state and prospects. Appl Microbiol Biotechnol 68:436–444

    CAS  PubMed  Google Scholar 

  • Vincenzini M, Ferrari F, Margheri MO, Florenzano G (1980) Quinoid and tocopherol levels in Spirulina platensis. Microbiologia 3:131–136

    CAS  Google Scholar 

  • Vismara R, Vestri S, Kusmic C, Brarsanti L, Gualtieri P (2003) Natural vitamin E enrichment of Artema salina fed freshwater and mirine microalge. J Appl Phycol 15:75–80

    CAS  Google Scholar 

  • Yoshida Y, Saito Y, Jones LS, Shigeri Y (2007) Chemical reactivities and physical effects in comparison between tocopherols and tocotrienols: Physiological significance and prospects as antioxidants. J Biosci Bioeng 104:439–445

    CAS  PubMed  Google Scholar 

  • Zhang K, Kurano N, Miyachi S (1999) Outdoor cultivation of a cyanobacterium with a vertical flat-plate photobioreactor: Effects on the productivity of the reactor orientation, distance setting, between the plates, and the culture temperature. Appl Microbiol Biotechnol 52:781–786

    CAS  Google Scholar 

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Correspondence to James C. Ogbonna.

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Ogbonna, J.C. Microbiological production of tocopherols: current state and prospects. Appl Microbiol Biotechnol 84, 217–225 (2009). https://doi.org/10.1007/s00253-009-2104-7

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