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Applied Microbiology and Biotechnology

, Volume 100, Issue 10, pp 4309–4321 | Cite as

Thraustochytrids as production organisms for docosahexaenoic acid (DHA), squalene, and carotenoids

  • Inga Marie AasenEmail author
  • Helga Ertesvåg
  • Tonje Marita Bjerkan Heggeset
  • Bin Liu
  • Trygve Brautaset
  • Olav Vadstein
  • Trond E. Ellingsen
Mini-Review

Abstract

Thraustochytrids have been applied for industrial production of the omega-3 fatty acid docosahexaenoic (DHA) since the 1990s. During more than 20 years of research on this group of marine, heterotrophic microorganisms, considerable increases in DHA productivities have been obtained by process and medium optimization. Strains of thraustochytrids also produce high levels of squalene and carotenoids, two other commercially interesting compounds with a rapidly growing market potential, but where yet few studies on process optimization have been reported. Thraustochytrids use two pathways for fatty acid synthesis. The saturated fatty acids are produced by the standard fatty acid synthesis, while DHA is synthesized by a polyketide synthase. However, fundamental knowledge about the relationship between the two pathways is still lacking. In the present review, we extract main findings from the high number of reports on process optimization for DHA production and interpret these in the light of the current knowledge of DHA synthesis in thraustochytrids and lipid accumulation in oleaginous microorganisms in general. We also summarize published reports on squalene and carotenoid production and review the current status on strain improvement, which has been hampered by the yet very few published genome sequences and the lack of tools for gene transfer to the organisms. As more sequences now are becoming available, targets for strain improvement can be identified and open for a system-level metabolic engineering for improved productivities.

Keywords

DHA Squalene Astaxanthin Biosynthesis Process development Genetic tools 

Notes

Compliance with ethical standards

The authors confirm that ethical principles have been followed in the manuscript preparation.

Funding

The work on thraustochytrids and microbial oil production at SINTEF and NTNU is funded by grants from The Research Council of Norway.

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. Abe E, Ikeda K, Nutahara E, Hayashi M, Yamashita A, Taguchi R, Doi K, Honda D, Okino N, Ito M (2014) Novel lysophospholipid acyltransferase PLAT1 of Aurantiochytrium limacinum F26-b responsible for generation of palmitate-docosahexaenoate-phosphatidylcholine and phosphatidylethanolamine. PLoS One 9:e102377CrossRefPubMedPubMedCentralGoogle Scholar
  2. Aki T, Hachida K, Yoshinaga M, Katai Y, Yamasaki T, Kawamoto S, Kakizono T, Maoka T, Shigeta S, Suzuki O, Ono K (2003) Thraustochytrid as a potential source of carotenoids. J Am Oil Chem Soc 80:789–794CrossRefGoogle Scholar
  3. Alvarez HM, Steinbüchel A (2002) Triacylglycerols in prokaryotic microorganisms. Appl Microbiol Biotechnol 60:367–376CrossRefPubMedGoogle Scholar
  4. Armenta RE, Burja A, Radianingtyas H, Barrow CJ (2006) Critical assessment of various techniques for the extraction of carotenoids and co-enzyme Q 10 from the thraustochytrid strain ONC-T18. J Agric Food Chem 54:9752–9758CrossRefPubMedGoogle Scholar
  5. Bailey RB, DiMasi D, Hansen JM, Mirrasoul PJ, Ruecker CM, Veeder GT, Kaneko T, Barclay WR (2003) Enhanced production of lipids containing polyunsaturated fatty acids by very high density cultures of eukaryotic microbes in fermentors. US Patent 6:607,900Google Scholar
  6. Bakes MJ, Nichols PD (1995) Lipid, fatty acid and squalene composition of liver oil from six species of deep-sea sharks collected in southern Australian waters. Comp Biochem Physiol B 110:267–275CrossRefGoogle Scholar
  7. Barclay W, Weaver C, Metz C, Hansen J (2010) Development of a docosahexaenoic acid production technology using Schizochytrium: historical perspective and update. In: Ratledge C, Cohen Z (eds) Single cell oils: microbial and algal oils, 2nd edn. AOCS Press, Urbana, pp. 75–96CrossRefGoogle Scholar
  8. Bayne ACV, Boltz D, Owen C, Betz J, Maia G, Azadi P, Archer-Hartmann S, Zirkle R, Lippmeier JC (2013) Vaccination against influenza with recombinant hemagglutinin expressed by Schizochytrium sp. confers protective immunity. PLoS One 8:e61790CrossRefPubMedPubMedCentralGoogle Scholar
  9. Berman J, Zorrilla-Lopez U, Farre G, Zhu CF, Sandmann G, Twyman RM, Capell T, Christou P (2015) Nutritionally important carotenoids as consumer products. Phytochem Rev 14:727–743CrossRefGoogle Scholar
  10. Burja AM, Radianingtyas H, Windust A, Barrow CJ (2006) Isolation and characterization of polyunsaturated fatty acid producing Thraustochytrium species: screening of strains and optimization of omega-3 production. Appl Microbiol Biotechnol 72:1161–1169CrossRefPubMedGoogle Scholar
  11. Carmona ML, Naganuma T, Yamaoka Y (2003) Identification by HPLC-MS of carotenoids of the Thraustochytrium CHN-1 strain isolated from the Seto Inland Sea. Biosci Biotechnol Biochem 67:884–888CrossRefPubMedGoogle Scholar
  12. Chaisawang M, Verduyn C, Chauvatcharin S, Suphantharika M (2012) Metabolic networks and bioenergetics of Aurantiochytrium sp. B-072 during storage lipids formation. Braz J Microbiol 43:1192–1205CrossRefPubMedPubMedCentralGoogle Scholar
  13. Chang G, Gao N, Tian G, Wu Q, Chang M, Wang X (2013a) Improvement of docosahexaenoic acid production on glycerol by Schizochytrium sp. S31 with constantly high oxygen transfer coefficient. Bioresour Technol 142:400–406CrossRefPubMedGoogle Scholar
  14. Chang G, Luo Z, Gu S, Wu Q, Chang M, Wang X (2013b) Fatty acid shifts and metabolic activity changes of Schizochytrium sp. S31 cultured on glycerol. Bioresour Technol 142:255–260CrossRefPubMedGoogle Scholar
  15. Chang G, Wu J, Jiang C, Tian G, Wu Q, Chang M, Wang X (2014) The relationship of oxygen uptake rate and kLa with rheological properties in high cell density cultivation of docosahexaenoic acid by Schizochytrium sp. S31. Bioresour Technol 152:234–240CrossRefPubMedGoogle Scholar
  16. Chaung KC, Chu CY, Su YM, Chen YM (2012) Effect of culture conditions on growth, lipid content, and fatty acid composition of Aurantiochytrium mangrovei strain BL10. AMB Express 2:42Google Scholar
  17. Cheng RB, Lin XZ, Wang ZK, Yang SJ, Rong H, Ma Y (2011) Establishment of a transgene expression system for the marine microalga Schizochytrium by 18S rDNA-targeted homologous recombination. World J Microbiol Biotechnol 27:737–741CrossRefGoogle Scholar
  18. Cheng R, Ma R, Li K, Rong H, Lin X, Wang Z, Yang S, Ma Y (2012) Agrobacterium tumefaciens mediated transformation of marine microalgae Schizochytrium. Microbiol Res 167:179–186CrossRefPubMedGoogle Scholar
  19. Chodchoey K, Verduyn C (2012) Growth, fatty acid profile in major lipid classes and lipid fluidity of Aurantiochytrium mangrovei SK-02 as a function of growth temperature. Braz J Microbiol 43:187–200CrossRefPubMedPubMedCentralGoogle Scholar
  20. Cutzu R, Coi A, Rosso F, Bardi L, Ciani M, Budroni M, Zara G, Zara S, Mannazzu I (2013) From crude glycerol to carotenoids by using a Rhodotorula glutinis mutant. World J Microbiol Biotechnol 29:1009–1017CrossRefPubMedGoogle Scholar
  21. Dulermo T, Lazar Z, Dulermo R, Rakicka M, Haddouche R, Nicaud JM (2015) Analysis of ATP-citrate lyase and malic enzyme mutants of Yarrowia lipolytica points out the importance of mannitol metabolism in fatty acid synthesis. Biochim Biophys Acta 1851:1107–1117CrossRefPubMedGoogle Scholar
  22. Ethier S, Woisard K, Vaughan D, Wen Z (2011) Continuous culture of the microalgae Schizochytrium limacinum on biodiesel-derived crude glycerol for producing docosahexaenoic acid. Bioresour Technol 102:88–93CrossRefPubMedGoogle Scholar
  23. Fan KW, Jiang Y, Faan YW, Chen F (2007) Lipid characterization of mangrove thraustochytrid — Schizochytrium mangrovei. J Agric Food Chem 55:2906–2910CrossRefPubMedGoogle Scholar
  24. FAO (2014) The state of world fisheries and aquaculture. Food and Agriculture Organization of the United Nations, Rome, 2014. E-ISBN 978–92-5-108276-8 (PDF)Google Scholar
  25. Ganuza E, Izquierdo MS (2007) Lipid accumulation in Schizochytrium G13/2S produced in continuous culture. Appl Microbiol Biotechnol 76:985–990CrossRefPubMedGoogle Scholar
  26. Garay LA, Boundy-Mills KL, German JB (2014) Accumulation of high-value lipids in single-cell microorganisms: a mechanistic approach and future perspectives. J Agric Food Chem 62:2709–2727CrossRefPubMedPubMedCentralGoogle Scholar
  27. Garcia-Vedrenne AE, Groner M, Page-Karjian A, Siegmund GF, Singhal S, Sziklay J, Roberts S (2013) Development of genomic resources for a thraustochytrid pathogen and investigation of temperature influences on gene expression. PLoS One 8:e74196CrossRefPubMedPubMedCentralGoogle Scholar
  28. Gassel S, Schewe H, Schmidt I, Schrader J, Sandmann G (2013) Multiple improvement of astaxanthin biosynthesis in Xanthophyllomyces dendrorhous by a combination of conventional mutagenesis and metabolic pathway engineering. Biotechnol Lett 35:565–569CrossRefPubMedGoogle Scholar
  29. Ghimire GP, Thuan NH, Koirala N, Sohng JK (2016) Advances in biochemistry and microbial production of squalene and its derivatives. J Microbiol Biotechnol 26:441–451Google Scholar
  30. Goold H, Beisson F, Peltier G, Li-Beisson Y (2015) Microalgal lipid droplets: composition, diversity, biogenesis and functions. Plant Cell Rep 34:545–555CrossRefPubMedGoogle Scholar
  31. Gupta A, Barrow CJ, Puri M (2012) Omega-3 biotechnology: thraustochytrids as a novel source of omega-3 oils. Biotechnol Adv 30:1733–1745CrossRefPubMedGoogle Scholar
  32. Hauvermale A, Kuner J, Rosenzweig B, Guerra D, Diltz S, Metz JG (2006) Fatty acid production in Schizochytrium sp.: involvement of a polyunsaturated fatty acid synthase and a type I fatty acid synthase. Lipids 41:739–747CrossRefPubMedGoogle Scholar
  33. Hoang MH, Ha NC, Thom le T, Tam LT, Anh HT, Thu NT, Hong DD (2014) Extraction of squalene as value-added product from the residual biomass of Schizochytrium mangrovei PQ6 during biodiesel producing process. J Biosci Bioeng 118:632–639CrossRefPubMedGoogle Scholar
  34. Honda D, Yokochi T, Nakahara T, Raghukumar S, Nakagiri A, Schaumann K, Higashihar T (1999) Molecular phylogeny of labyrinthulids and thraustochytrids based on the sequencing of 18S ribosomal RNA gene. J Eukaryot Microbiol 46:637–647CrossRefPubMedGoogle Scholar
  35. Hong WK, Heo SY, Oh BR, Kim CH, Sohn JH, Yang JW, Kondo A, Seo JW (2013a) A transgene expression system for the marine microalgae Aurantiochytrium sp. KRS101 using a mutant allele of the gene encoding ribosomal protein L44 as a selectable transformation marker for cycloheximide resistance. Bioprocess Biosyst Eng 36:1191–1197CrossRefPubMedGoogle Scholar
  36. Hong WK, Heo SY, Park HM, Kim CH, Sohn JH, Kondo A, Seo JW (2013b) Characterization of a squalene synthase from the thraustochytrid microalga Aurantiochytrium sp. KRS101. J Microbiol Biotechnol 23:759–765CrossRefPubMedGoogle Scholar
  37. Huang ZR, Lin YK, Fang YE (2009) Biological and pharmacological activities of squalene and related compounds: potential uses in cosmetic dermatology. Molecules 14:540–554CrossRefPubMedGoogle Scholar
  38. Huang TY, Lu WC, Chu IM (2012) A fermentation strategy for producing docosahexaenoic acid in Aurantiochytrium limacinum SR21 and increasing C22:6 proportions in total fatty acid. Bioresour Technol 123:8–14CrossRefPubMedGoogle Scholar
  39. Jakobsen AN, Aasen IM, Josefsen KD, Strøm AR (2008) Accumulation of docosahexaenoic acid-rich lipid in thraustochytrid Aurantiochytrium sp. strain T66: effects of N and P starvation and O2 limitation. Appl Microbiol Biotechnol 80:297–306CrossRefPubMedGoogle Scholar
  40. Janthanomsuk P, Verduyn C, Chauvatcharin S (2015) Improved docosahexaenoic acid production in Aurantiochytrium by glucose limited pH-auxostat fed-batch cultivation. Bioresour Technol 196:592–599CrossRefPubMedGoogle Scholar
  41. Ji XJ, Mo KQ, Ren LJ, Li GL, Huang JZ, Huang H (2015) Genome sequence of Schizochytrium sp. CCTCC M209059, an effective producer of docosahexaenoic acid-rich lipids. Genome Announc 3:e00819–e00815CrossRefPubMedPubMedCentralGoogle Scholar
  42. Karas BJ, Diner RE, Lefebvre SC, McQuaid J, Phillips AP, Noddings CM, Brunson JK, Valas RE, Deerinck TJ, Jablanovic J, Gillard JT, Beeri K, Ellisman MH, Glass JI, Hutchison CA, Smith HO, Venter JC, Allen AE, Dupont CL, Weyman PD (2015) Designer diatom episomes delivered by bacterial conjugation. Nat Commun 6:692CrossRefGoogle Scholar
  43. Kaya K, Nakazawa A, Matsuura H, Honda D, Inouye I, Watanabe MM (2011) Thraustochytrid Aurantiochytrium sp. 18 W-13a accumulates high amounts of squalene. Biosci Biotechnol Biochem 75:2246–2248CrossRefPubMedGoogle Scholar
  44. Kim S, Lee YC, Cho DH, Lee HU, Huh YS, Kim GJ, Kim HS (2014) A simple and non-invasive method for nuclear transformation of intact-walled Chlamydomonas reinhardtii. PLoS One 9:e101018CrossRefPubMedPubMedCentralGoogle Scholar
  45. Li J, Liu R, Chang G, Li X, Chang M, Liu Y, Jin Q, Wang X (2015) A strategy for the highly efficient production of docosahexaenoic acid by Aurantiochytrium limacinum SR21 using glucose and glycerol as the mixed carbon sources. Bioresour Technol 177:51–57CrossRefPubMedGoogle Scholar
  46. Lippmeier JC, Crawford KS, Owen CB, Rivas AA, Metz JG, Apt KE (2009) Characterization of both polyunsaturated fatty acid biosynthetic pathways in Schizochytrium sp. Lipids 44:621–630CrossRefPubMedGoogle Scholar
  47. Ma Z, Tan Y, Cui G, Feng Y, Cui Q, Song X (2015) Transcriptome and gene expression analysis of DHA producer Aurantiochytrium under low temperature conditions. Sci Report 5:14446CrossRefGoogle Scholar
  48. Matsuda T, Sakaguchi K, Kobayashi T, Abe E, Kurano N, Sato A, Okita Y, Sugimoto S, Hama Y, Hayashi M, Okino N, Ito M (2011) Molecular cloning of a Pinguiochrysis pyriformis oleate-specific microsomal delta12-fatty acid desaturase and functional analysis in yeasts and thraustochytrids. J Biochem 150:375–383CrossRefPubMedGoogle Scholar
  49. Matsuda T, Sakaguchi K, Hamaguchi R, Kobayashi T, Abe E, Hama Y, Hayashi M, Honda D, Okita Y, Sugimoto S, Okino N, Ito M (2012) Analysis of Δ12-fatty acid desaturase function revealed that two distinct pathways are active for the synthesis of PUFAs in T. aureum ATCC 34304. J Lipid Res 53:1210–1222CrossRefPubMedPubMedCentralGoogle Scholar
  50. Metz JG, Roessler P, Facciotti D, Levering C, Dittrich F, Lassner M, Valentine R, Lardizabal K, Domergue F, Yamada A, Yazawa K, Knauf V, Browse J (2001) Production of polyunsaturated fatty acids by polyketide synthases in both prokaryotes and eukaryotes. Science 293:290–293CrossRefPubMedGoogle Scholar
  51. Mühlroth A, Li K, Røkke G, Winge P, Olsen Y, Hohmann-Marriott MF, Vadstein O, Bones AM (2013) Pathways of lipid metabolism in marine algae, co-expression network, bottlenecks and candidate genes for enhanced production of EPA and DHA in species of Chromista. Mar Drugs 11:4662–4697CrossRefPubMedPubMedCentralGoogle Scholar
  52. Nakazawa A, Matsuura H, Kose R, Kato S, Honda D, Inouye I, Kaya K, Watanabe MM (2012) Optimization of culture conditions of the thraustochytrid Aurantiochytrium sp. strain 18 W-13a for squalene production. Bioresour Technol 109:287–291CrossRefPubMedGoogle Scholar
  53. Nakazawa A, Kokubun Y, Matsuura H, Yonezawa N, Kose R, Yoshida M, Tanabe Y, Kusuda E, Van Thang D, Ueda M, Honda D, Mahakhant A, Kaya K, Watanabe MM (2014) TLC screening of thraustochytrid strains for squalene production. J Appl Phycol 26:29–41CrossRefGoogle Scholar
  54. Olsen Y (2011) Resources for fish feed in future mariculture. Aquac Environ Int 1:187–200CrossRefGoogle Scholar
  55. Popa O, Babeanu NE, Popa I, Nita S, Dinu-Parvu CE (2015) Methods for obtaining and determination of squalene from natural sources. Biomed Res Int 2015:367202CrossRefPubMedPubMedCentralGoogle Scholar
  56. Qu L, Ji XJ, Ren LJ, Nie ZK, Feng Y, Wu WJ, Ouyang PK, Huang H (2011) Enhancement of docosahexaenoic acid production by Schizochytrium sp. using a two-stage oxygen supply control strategy based on oxygen transfer coefficient. Lett Appl Microbiol 52:22–27CrossRefPubMedGoogle Scholar
  57. Qu L, Ren LJ, Li J, Sun GN, Ji XJ, Nie ZK, Huang H (2013a) Biomass composition, lipid characterization, and metabolic profile analysis of the fed-batch fermentation process of two different docosahexaenoic acid producing Schizochytrium sp. strains. Appl Biochem Biotechnol 171:1865–1876CrossRefPubMedGoogle Scholar
  58. Qu L, Ren LJ, Sun GN, Ji XJ, Nie ZK, Huang H (2013b) Batch, fed-batch and repeated fed-batch fermentation processes of the marine thraustochytrid Schizochytrium sp. for producing docosahexaenoic acid. Bioprocess Biosyst Eng 36:1905–1912CrossRefPubMedGoogle Scholar
  59. Quilodran B, Hinzpeter I, Hormazabal E, Quiroz A, Shene C (2010) Docosahexaenoic acid (C22:6n-3, DHA) and astaxanthin production by Thraustochytriidae sp. AS4-A1, a native strain with high similitude to Ulkenia sp.: evaluation of liquid residues from food industry as nutrient sources. Enzym Microb Technol 47:24–30CrossRefGoogle Scholar
  60. Raghukumar S (2002) Ecology of the marine protists, the Labyrinthulomycetes (thraustochytrids and labyrinthulids). Eur J Protistol 38:127–145CrossRefGoogle Scholar
  61. Raghukumar S (2008) Thraustochytrid marine protists: production of PUFAs and other emerging technologies. Mar Biotechnol 10:631–640CrossRefPubMedGoogle Scholar
  62. Ratledge C (2002) Regulation of lipid accumulation in oleaginous microorganisms. Biochem Soc T 30:1047–1050CrossRefGoogle Scholar
  63. Ratledge C (2004) Fatty acid biosynthesis in microorganisms being used for single cell oil production. Biochimie 86:807–815CrossRefPubMedGoogle Scholar
  64. Ratledge C (2014) The role of malic enzyme as the provider of NADPH in oleaginous microorganisms: a reappraisal and unsolved problems. Biotechnol Lett 36:1557–1568CrossRefPubMedGoogle Scholar
  65. Ratledge C, Wynn JP (2002) The biochemistry and molecular biology of lipid accumulation in oleaginous microorganisms. Adv Appl Microbiol 51:1–51CrossRefPubMedGoogle Scholar
  66. Reddy LH, Couvreur P (2009) Squalene: a natural triterpene for use in disease management and therapy. Adv Drug Deliv Rev 61:1412–1426CrossRefPubMedGoogle Scholar
  67. Ren LJ, Huang H, Xiao AH, Lian M, Jin LJ, Ji XJ (2009) Enhanced docosahexaenoic acid production by reinforcing acetyl-CoA and NADPH supply in Schizochytrium sp. HX-308. Bioprocess Biosyst Eng 32:837–843CrossRefPubMedGoogle Scholar
  68. Ren LJ, Ji XJ, Huang H, Qu L, Feng Y, Tong QQ, Ouyang PK (2010) Development of a stepwise aeration control strategy for efficient docosahexaenoic acid production by Schizochytrium sp. Appl Microbiol Biotechnol 87:1649–1656CrossRefPubMedGoogle Scholar
  69. Ren LJ, Feng Y, Li J, Qu L, Huang H (2013) Impact of phosphate concentration on docosahexaenoic acid production and related enzyme activities in fermentation of Schizochytrium sp. Bioprocess Biosyst Eng 36:1177–1183CrossRefPubMedGoogle Scholar
  70. Ren LJ, Sun GN, Ji XJ, Hu XC, Huang H (2014a) Compositional shift in lipid fractions during lipid accumulation and turnover in Schizochytrium sp. Bioresour Technol 157:107–113CrossRefPubMedGoogle Scholar
  71. Ren LJ, Sun LN, Zhuang XY, Qu L, Ji XJ, Huang H (2014b) Regulation of docosahexaenoic acid production by Schizochytrium sp.: effect of nitrogen addition. Bioprocess Biosyst Eng 37:865–872CrossRefPubMedGoogle Scholar
  72. Rubin E, Tanguy A, Perrigault M, Pales Espinosa E, Allam B (2014) Characterization of the transcriptome and temperature-induced differential gene expression in QPX, the thraustochytrid parasite of hard clams. BMC Genomics 15:245CrossRefPubMedPubMedCentralGoogle Scholar
  73. Sakaguchi K, Matsuda T, Kobayashi T, Ohara J, Hamaguchi R, Abe E, Nagano N, Hayashi M, Ueda M, Honda D, Okita Y, Taoka Y, Sugimoto S, Okino N, Ito M (2012) Versatile transformation system that is applicable to both multiple transgene expression and gene targeting for thraustochytrids. Appl Environ Microbiol 78:3193–3202CrossRefPubMedPubMedCentralGoogle Scholar
  74. Schmidt I, Schewe H, Gassel S, Jin C, Buckingham J, Hümbelin M, Sandmann G, Schrader J (2011) Biotechnological production of astaxanthin with Phaffia rhodozyma/Xanthophyllomyces dendrorhous. Appl Microbiol Biotechnol 89:555–571CrossRefPubMedGoogle Scholar
  75. Singh P, Liu Y, Li LS, Wang GY (2014) Ecological dynamics and biotechnological implications of thraustochytrids from marine habitats. Appl Microbiol Biotechnol 98:5789–5805CrossRefPubMedGoogle Scholar
  76. Song X, Tan Y, Liu Y, Zhang J, Liu G, Feng Y, Cui Q (2013) Different impacts of short-chain fatty acids on saturated and polyunsaturated fatty acid biosynthesis in Aurantiochytrium sp. SD116. J Agric Food Chem 61:9876–9881CrossRefPubMedGoogle Scholar
  77. Suen YL, Tang H, Huang J, Chen F (2014) Enhanced production of fatty acids and astaxanthin in Aurantiochytrium sp. by the expression of Vitreoscilla hemoglobin. J Agric Food Chem 62:12392–12398CrossRefPubMedGoogle Scholar
  78. Sun L, Ren L, Zhuang X, Ji X, Yan J, Huang H (2014) Differential effects of nutrient limitations on biochemical constituents and docosahexaenoic acid production of Schizochytrium sp. Bioresour Technol 159:199–206CrossRefPubMedGoogle Scholar
  79. Sun H, Chen H, Zang X, Hou P, Zhou B, Liu Y, Wu F, Cao X, Zhang X (2015) Application of the cre/loxP site-specific recombination system for gene transformation in Aurantiochytrium limacinum. Molecules 20:10110–10121CrossRefPubMedGoogle Scholar
  80. Taoka Y, Nagano N, Okita Y, Izumida H, Sugimoto S, Hayashi M (2009) Influences of culture temperature on the growth, lipid content and fatty acid composition of Aurantiochytrium sp. strain mh0186. Mar Biotechnol 11:368–374CrossRefPubMedGoogle Scholar
  81. Unagul P, Assantachai C, Phadungruengluij S, Suphantharika M, Verduyn C (2005) Properties of the docosahexaenoic acid-producer Schizochytrium mangrovei Sk-02: effects of glucose, temperature and salinity and their interaction. Bot Mar 48:387–394CrossRefGoogle Scholar
  82. Valentine RC, Valentine DL (2004) Omega-3 fatty acids in cellular membranes: a unified concept. Prog Lipid Res 43:383–400CrossRefPubMedGoogle Scholar
  83. Wang CW (2015) Lipid droplet dynamics in budding yeast. Cell Mol Life Sci 72:2677–2695CrossRefPubMedGoogle Scholar
  84. Xie Y, Wang G (2015) Mechanisms of fatty acid synthesis in marine fungus-like protists. Appl Microbiol Biotechnol 99:8363–8375CrossRefPubMedGoogle Scholar
  85. Yaguchi T, Tanaka S, Yokochi T, Nakahara T, Higashihara T (1997) Production of high yields of docosahexaenoic acid by Schizochytrium sp. strain SR21. J Am Oil Chem Soc 74:1431–1434CrossRefGoogle Scholar
  86. Yamasaki T, Aki T, Shinozaki M, Taguchi M, Kawamoto S, Ono K (2006) Utilization of Shochu distillery wastewater for production of polyunsaturated fatty acids and xanthophylls using thraustochytrid. J Biosci Bioeng 102:323–327CrossRefPubMedGoogle Scholar
  87. Yan J, Cheng R, Lin X, You S, Li K, Rong H, Ma Y (2013) Overexpression of acetyl-CoA synthetase increased the biomass and fatty acid proportion in microalga Schizochytrium. Appl Microbiol Biotechnol 97:1933–1939CrossRefPubMedGoogle Scholar
  88. Ye C, Qiao W, Yu X, Ji X, Huang H, Collier JL, Liu L (2015) Reconstruction and analysis of the genome-scale metabolic model of Schizochytrium limacinum SR21 for docosahexaenoic acid production. BMC Genomics 16:799CrossRefPubMedPubMedCentralGoogle Scholar
  89. Yokoyama R, Honda D (2007) Taxonomic rearrangement of the genus Schizochytrium sensu lato based on morphology, chemotaxonomic characteristics, and 18S rRNA gene phylogeny (Thraustochytriaceae, Labyrinthulomycetes): emendation for Schizochytrium and erection of Aurantiochytrium and Oblongichytrium gen. nov. Mycoscience 48:199–211CrossRefGoogle Scholar
  90. Yokoyama R, Salleh B, Honda D (2007) Taxonomic rearrangement of the genus Ulkenia sensu lato based on morphology, chemotaxonomical characteristics, and 18S rRNA gene phylogeny (Thraustochytriaceae, Labyrinthulomycetes): emendation for Ulkenia and erection of Botryochytrium, Parietichytrium, and Sicyoidochytrium gen. nov. Mycoscience 48:329–341CrossRefGoogle Scholar
  91. Zeng Y, Ji XJ, Lian M, Ren LJ, Jin LJ, Ouyang PK, Huang H (2011) Development of a temperature shift strategy for efficient docosahexaenoic acid production by a marine fungoid protist, Schizochytrium sp. HX-308. Appl Biochem Biotechnol 164:249–255CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Inga Marie Aasen
    • 1
    Email author
  • Helga Ertesvåg
    • 2
  • Tonje Marita Bjerkan Heggeset
    • 1
  • Bin Liu
    • 2
  • Trygve Brautaset
    • 1
    • 2
  • Olav Vadstein
    • 2
  • Trond E. Ellingsen
    • 1
  1. 1.Department of Biotechnology and NanomedicineSINTEF Materials and ChemistryTrondheimNorway
  2. 2.Department of BiotechnologyThe Norwegian University of Science and TechnologyTrondheimNorway

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