Fungal arachidonic acid-rich oil: Research, development and industrialization

Critical Reviews in Biotechnology

Volumn 34, Issue 3, 2014, Pages 197-214

  Ji, Xiao Jun ^a   Ren, Lu Jing ^a   Nie, Zhi Kui ^a   Huang, He ^a   Ouyang, Ping Kai ^a  

^a NANJING TECH UNIVERSITY   (China)

Author keywords

Arachidonic acid; Industrialization; Lipid accumulation; Mortierella; Oleaginous fungi; Polyunsaturated fatty acid; Triacylglycerol

Indexed keywords

FUNGI; POLYUNSATURATED FATTY ACIDS;

ARACHIDONIC ACIDS; INDUSTRIALIZATION; LIPID ACCUMULATIONS; MORTIERELLA; OLEAGINOUS FUNGI; TRIACYLGLYCEROLS;

OIL SHALE;

ARACHIDONIC ACID; OIL; POLYUNSATURATED FATTY ACID; TRIACYLGLYCEROL;

BIOCHEMISTRY; BIOSYNTHESIS; DNA MODIFICATION; DOWNSTREAM PROCESSING; FERMENTATION; FUNGUS; FUNGUS CULTURE; MORTIERELLA; NONHUMAN; PRIORITY JOURNAL; REVIEW; INDUSTRY; METABOLISM; RESEARCH;

ARACHIDONIC ACID; FUNGI; INDUSTRY; OILS; RESEARCH;

EID: 84898545025     PISSN: 07388551     EISSN: 15497801     Source Type: Journal    
DOI: 10.3109/07388551.2013.778229     Document Type: Review

References (163)

1. Aki T, Nagahata Y, Ishihara K, et al. (2001). Production of arachidonic acid by filamentous fungus, Mortierella alliacea strain YN-15. J Am Oil Chem Soc, 78, 599-604.
2. Akimoto K, Higashiyama K, Shimizu S. (2000). Production of arachidonic acid-containing lipid and dihomo-g-linolenic acid-containing lipid. JP Patent, 2000069987.
3. Amano N, Shinmen Y, Akimoto K, et al. (1992). Chemotaxonomic significance of fatty acid composition in the genus Mortierella (Zygomycetes, Mortierellaceae). Mycotaxon, 94, 257-65.
4. Ando A, Sumida Y, Negoro H, et al. (2009). Establishment of Agrobacterium tumefaciens-mediated transformation of an oleaginous fungus, Mortierella alpina 1S-4, and its application for eicosapentaenoic acid producer breeding. Appl Environ Microbiol, 75, 5529-35.
5. Archer DB, Connerton IF, MacKenzie DA. (2008). Filamentous fungi for production of food additives and processing aids. Adv Biochem Eng Biotechnol, 111, 99-147.
6. Athenstaedt K, Daum G. (1999). Phosphatidic acid, a key intermediate in lipid metabolism. Eur J Biochem, 266, 1-16.
7. Bajpai PK, Bajpai P, Ward OP. (1991a). Arachidonic acid production by fungi. Appl Environ Microbiol, 57, 1255-8.
8. Bajpai P, Bajpai PK, Ward OP. (1991b). Effects of aging Mortierella mycelium on production of arachidonic and eicosapentaenoic acids. J Am Oil Chem Soc, 68, 775-80.
9. Bajpai PK, Bajpai P, Ward OP. (1991c). Production of arachidonic acid by Mortierella alpina ATCC 32222. J Ind Microbiol Biotechnol, 8, 179-85.
10. Barclay WR. (2010). Method for arachidonic acid production. US Patent 7736885.
11. Beaudoin F, Michaelson LV, Hey SJ, et al. (2000). Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway. Proc Natl Acad Sci USA, 97, 6421-6.
12. Bigogno C, Khozin-Goldberg I, Adlerstein D, Cohen Z. (2002). Biosynthesis of arachidonic acid in the oleaginous microalga Parietochloris incisa (Chlorophyceae): radiolabeling studies. Lipids, 37, 209-16.
13. Boswell K, Koskelo EK, Carl L, et al. (1996). Preclinical evaluation of single-cell oils that are highly enriched with arachidonic acid and docosahexaenoic acid. Food Chem Toxicol, 34, 585-93.
14. Botha A, Paul I, Roux C, et al. (1999). An isolation procedure for arachidonic acid producing Mortierella species. Antonie van Leeuwenhoek, 75, 253-6.
15. Bresson JL, Flynn A, Heinonen M, et al. (2008). Scientific opinion of the Panel on Dietetic Products Nutrition and Allergies on a request from the European Commission on the safety of fungal oil from Mortierella alpina. The EFSA J, 770, 1-15.
16. Burns RA., Wibert GJ, Diersen-Schade DA, Kelly CM. (1999). Evaluation of single-cell sources of docosahexaenoic acid and arachidonic acid: 3-month rat oral safety study with an in utero phase. Food Chem Toxicol, 37, 23-36.
17. Calder PC. (2008). Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res, 52, 885-97.
18. Casterton PL, Curry LL, Lina BAR, et al. (2009). 90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil. Food Chem Toxicol, 47, 2407-18.
19. Čertík M, Sakuradani E, Shimizu S. (1998). Desaturase-defective fungal mutants: useful tools for the regulation and overproduction of polyunsaturated fatty acids. Trends Biotechnol, 16, 500-5.
20. Čertík M, Shimizu S. (1999). Biosynthesis and regulation of microbial polyunsaturated fatty acid production. J Biosci Bioeng, 87, 1-14.
21. Chaudhuri S, Ghosh S, Bhattacharyya D, Bandyopadhyay S. (1998). Effect of mustard meal on the production of arachidonic acid by Mortierella elongata SC-208. J Am Oil Chem Soc, 75, 1053-5.
22. Chen H, Chang C, Chen C. (1997). Optimization of arachidonic acid production by Mortierella alpina Wuji-H4 isolate. J Am Oil Chem Soc, 74, 569-78.
23. Chen R, Matsui K, Ogawa M, et al. (2006). Expression of D6, D5 desaturase and GLELO elongase genes from Mortierella alpina for production of arachidonic acid in soybean seeds. Plant Sci, 170, 399-406.
24. Cheng MH, Walker TH, Hulbert GJ, Raman DR. (1999). Fungal production of eicosapentaenoic and arachidonic acids from industrial waste streams and crude soybean oil. Bioresour Technol, 67, 101-10.
25. Coleman RA, Lee DP. (2004). Enzymes of triacylglycerol synthesis and their regulation. Progr Lipid Res, 43, 134-76.
26. Courchesne NMD, Parisien A, Wang B, Lan CQ. (2009). Enhancement of lipid production using biochemical, genetic and transcription factor engineering approaches. J Biotechnol, 141, 31-41.
27. Damude HG, Gillies PJ, Macool DJ, et al. (2005). High arachidonic acid producing strains of Yarrowia lipolytica. US patent 7588931.
28. Davies RJ, Holdsworth JE. (1992). Synthesis of lipids in yeasts: biochemistry, physiology and production. Adv Appl Lipid Res, 1, 119-59.
29. De Bell R, Jack R. (1975). Stereospecific analysis of major glycerolipids of Phycomyces blakesleeanus sporiangiophores and mycelium. J Bacteriol, 124, 220-4.
30. Dedyukhina EG, Chistyakova TI, Kamzolova SV, et al. (2012). Arachidonic acid synthesis by glycerol-grown Mortierella alpina. Eur J Lipid Sci Technol, 144, 833-41.
31. Dedyukhina EG, Chistyakova TI, Vainshtein MB. (2011). Biosynthesis of arachidonic acid by micromycetes (review). Appl Biochem Microbiol, 47, 109-17.
32. Dyal SD, Narine SS. (2005). Implications for the use of Mortierella fungi in the industrial production of essential fatty acids. Food Res Int, 38, 445-67.
33. Eroshin VK, Dedyukhina EG, Chistyakova TI, et al. (1996a). Studies on arachidonic acid production by Mortierella fungi: a microbiological method for selecting arachidonic acid producers. Microbiology, 65, 26-31.
34. Eroshin VK, Dedyukhina EG, Chistyakova TI, et al. (1996b). Arachidonic acid production by species of Mortierella. World J Microbiol Biotechnol, 12, 91-6.
35. Eroshin VK, Satroutdinov AD, Dedyukhina EG, Chistyakova TI. (2000). Arachidonic acid production by Mortierella alpina with growthcoupled lipid synthesis. Process Biochem, 35, 1171-5.
36. Fakas S, Papanikolaou S, Galiotou-Panayotou M, et al. (2009). Biochemistry and biotechnology of single cell oil. In: Pandey A, Larroche C, eds. New Horizons in Biotechnology. New Delhi: AsiaTech Publishers Inc, 38-60.
37. Gams W. (1977). A key to the species of Mortierella. Persoonia, 9, 381-91.
38. Gangar A, Karande AA, Rajasekharan R. (2001). Purification and characterization of acyl-acyl carrier protein synthetase from oleaginous yeast and its role in triacylglycerol biosynthesis. Biochem J, 360, 471-9.
39. Hamanaka T, Higashiyama K, Fujikawa S, Park EY. (2001). Mycelial pellet intrastructure and visualization of mycelia and intracellular lipid in a culture of Mortierella alpina. Appl Microbiol Biotechnol, 56, 233-8.
40. Hansson L, Dostálek M. (1988). Effect of culture conditions on mycelial growth and production of g-linolenic acid by the fungus Mortierella ramanniana. Appl Microbiol Biotechnol, 28, 240-6.
41. Hempenius RA, Van-Delft JM, Prinsen M, Lina BA. (1997). Preliminary safety assessment of an arachidonic acid-enriched oil derived from Mortierella alpina: summary of toxicological data. Food Chem Toxicol, 35, 573-81.
42. Higashiyama K. (2003). Industrial production of arachidonic acid by filamentous fungus, Mortierella. Recent Res Devel Biotechnol Bioeng, 5, 79-95.
43. Higashiyama K, Fujikawa S, Park EY, Okabe M. (1999a). Image analysis of morphological change during arachidonic acid production by Mortierella alpina 1S-4. J Biosci Bioeng, 87, 489-94.
44. Higashiyama K, Fujikawa S, Park EY, Shimizu S. (2002). Production of arachidonic acid by Mortierella fungi. Biotechnol Bioproc Eng, 7, 252-62.
45. Higashiyama K, Murakami K, Tsujimura H, et al. (1999b). Effects of dissolved oxygen on the morphology of an arachidonic acid production by Mortierella alpina 1S-4. Biotechnol Bioeng, 63, 442-8.
46. Higashiyama K, Yaguchi T, Akimoto K, et al. (1998a). Effects of mineral addition on the growth morphology of and arachidonic acid production by Mortierella alpina 1S-4. J Am Oil Chem Soc, 75, 1815-19.
47. Higashiyama K, Yaguchi T, Akimoto K, et al. (1998b). Enhancement of arachidonic acid production by Mortierella alpina 1S-4. J Am Oil Chem Soc, 75, 1501-5.
48. Ho SY, Chen F. (2008). Lipid characterization of Mortierella alpina grown at different NaCl concentrations. J Agric Food Chem, 56, 7903-9.
49. Ho SY, Jiang Y, Chen F. (2007). Polyunsaturated fatty acids (PUFAs) content of the fungus Mortierella alpina isolated from soil. J Agric Food Chem, 55, 3960-6.
50. Hou C. (2008). Production of arachidonic acid and dihomo-g-linolenic acid from glycerol by oil-producing filamentous fungi, Mortierella in the ARS culture collection. J Ind Microbiol Biotechnol, 35, 501-6.
51. Hwang BH, Kim JW, Park CY, et al. (2005). High-level production of arachidonic acid by fed-batch culture of Mortierella alpina using NH4OH as a nitrogen source and pH control. Biotechnol Lett, 27, 731-5.
52. Jackson FM, Michaelson L, Fraser T, et al. (1998). Biosynthesis of triacylglycerol in the filamentous fungus Mucor circinelloides. Microbiology, 144, 2639-45.
53. Jang HD, Lin YY, Yang SS. (2005). Effect of culture media and conditions on polyunsaturated fatty acids production by Mortierella alpina. Bioresour Technol, 96, 1633-44.
54. Jareonkitmongkol S, Kawashima H, Shirasaka N, et al. (1992). Production of dihomo-g-linolenic acid by a D5-desaturase-defective mutant of Mortierella alpina 1S-4. Appl Environ Microbiol, 58, 2196-200.
55. Ji XJ, Huang H, Nie ZK, et al. (2012). Fuels and chemicals from hemicellulose sugars. Adv Biochem Engin Biotechnol, 128, 199-224.
56. Jin MJ, Huang H, Xiao AH, et al. (2008). A novel two-step fermentation process for improved arachidonic acid production by Mortierella alpina. Biotechnol Lett, 30, 1087-91.
57. Jin MJ, Huang H, Xiao AH, et al. (2009). Enhancing arachidonic acid production by Mortierella alpina ME-1 using improved mycelium aging technology. Bioproc Biosyst Eng, 32, 117-22.
58. Jin MJ, Huang H, Zhang K, et al. (2007). Metabolic flux analysis on arachidonic acid fermentation. Frontiers Chem Eng China, 1, 421-6.
59. Kawashima H, Akimoto K, Higashiyama K, et al. (2000). Industrial production of dihomo-g-linolenic acid by a D5 desaturase-defective mutant of Mortierella alpina 1S-4 fungus. J Am Oil Chem Soc, 77, 1135-9.
60. Kawashima H, Kamada N, Sakuradani E, et al. (1997). Production of 8,11,14,17-cis-eicosatetraenoic acid by D5 desaturase-defective mutants of an arachidonic acid-producing fungus, Mortierella alpina. J Am Oil Chem Soc, 74, 455-9.
61. Kazuhiko S, Keita S, Yoshimasa T, Eisei T. (1989). Skin external preparation. JP Patent 1038007.
62. Kendrick A, Ratledge C. (1992). Desaturation of polyunsaturated fatty acids in Mucor circinelloides and the involvement of a novel membrane-bound malic enzyme. Eur J Biochem, 209, 667-73.
63. Koike Y, Hong JC, Higashiyama K, et al. (2001). Effect of consumed carbon to nitrogen ratio of mycelial morphology and arachidonic acid production in cultures of Mortierella alpina. J Biosci Bioeng, 91, 382-9.
64. Koizumi K, Higashiyama K, Park EY. (2006). Effects of amino acid on morphological development and nucleus formation of arachidonic acid-producing filamentous microorganism, Mortierella alpina. J Appl Microbiol, 100, 885-92.
65. Kosa M, Ragauskas AJ. (2011). Lipids from heterotrophic microbes: advances in metabolism research. Trends Biotechnol, 29, 53-61.
66. Koskelo EK, Boswell K, Carl L, et al. (1997). High levels of dietary arachidonic acid triglyceride exhibit no subchronic toxicity in rats. Lipids, 32, 397-405.
67. Kyle DJ. (1997a). Arachidonic acid and methods for the production and use thereof. US Patent 5658767.
68. Kyle DJ. (1997b). Production and use of a single cell oil highly enriched in arachidonic acid. Lipid Technol, 9, 116-21.
69. Kyle DJ. (2003). Arachidonic acid and methods for the production and use thereof. European Patent Application 1,342,787.
70. Kyle DJ. (2008). Microalgal feeds containing arachidonic acid and their production and use. US Patent No. 7396548.
71. Kyle DJ. (2010). The future development of single cell oils. In: Cohen Z, Ratledge C, eds. Single Cell Oils: Microbial and Algal Oils. 2nd ed. Champaign: AOCS Press, 439-51.
72. Lan WZ, Qin WM, Yu LJ. (2002). Effect of glutamate on arachidonic acid production from Mortierella alpina. Lett Appl Microbiol, 35, 357-60.
73. Laoteng K, Čertík M, Cheevadhanark S. (2011). Mechanisms controlling lipid accumulation and polyunsaturated fatty acid synthesis in oleaginous fungi. Chem Papers, 65, 97-103.
74. Li YT, Li MT, Fu CH, et al. (2009). Improvement of arachidonic acid and eicosapentaenoic acid production by increasing the copy number of the genes encoding fatty acid desaturase and elongase into Pichia pastoris. Biotechnol Lett, 31, 1011-17.
75. Li ZY, Lu Y, Yadward VB, Ward OP. (1995). Process for production of arachidonic acid concentrate by a strain of Mortierella alpina. Can J Chem Eng, 73, 135-9.
76. Lindberg AM, Molin G. (1993). Effect of temperature and glucose supply on the production of polyunsaturated fatty acids by fungus Mortierella alpina CBS343.66 in fermentor cultures. Appl Microbiol Biotechnol, 39, 450-5.
77. Lu JM, Peng C, Ji XJ, et al. (2011). Fermentation characteristics of Mortierella alpina in response to different nitrogen sources. Appl Biochem Biotechnol, 164, 979-90.
78. Mackenzie DA, Wongwathanarat P, Carter AT, Archer DB. (2000). Isolation and use of a homologous histone H4 promoter and a ribosomal DNA region in a transformation vector for the oilproducing fungus Mortierella alpina. Appl Environ Microbiol, 66, 4655-61.
79. Metz JG, Roessler P, Facciotti D, et al. (2001). Polyketide synthases produce polyunsaturated fatty acids in both prokaryotes and eukaryotes. Science, 293, 290-3.
80. Michaelson LV, Lazarus CM, Griffiths G, et al. (1998). Isolation of a D5-fatty acid desaturase gene from Mortierella alpina. J Biol Chem, 273, 19055-9.
81. Mukhopadhyay M, Singh A, Banerjee R. (2012). Oleaginous fungi: a solution to oil crisis. In: Satyanarayana T, Johri BN, Prakash A, eds. Microorganisms in Environmental Management. Heidelberg: Springer, 403-14.
82. Murphy DJ. (2001). The biogenesis and functions of lipid bodies in animals, plants and microorganisms. Progr Lipid Res, 40, 325-438.
83. Myher J, Kuksis A, Geher K, et al. (1996). Stereospecific analysis of triacylglycerols rich in long-chain polyunsaturated fatty acids. Lipids, 31, 207-15.
84. Nisha A, Venkateswaran G. (2011). Effect of culture variables on mycelial arachidonic acid production by Mortierella alpina. Food Bioproc Technol, 4, 232-40.
85. Ochiai M, Kawashima H, Shimizu S. (2007). Method of breeding lipidproducing fungus. US Patent 20070072275.
86. Ochiai M, Kawashima H, Shimizu S, Sakuradani E. (2008). Breeding method of lipid producing fungi and use of such a method. US Patent 20080138874.
87. Papanikolaou S, Aggelis G. (2011). Lipids of oleaginous yeasts. Part I: biochemistry of single cell oil production. Eur J Lipid Sci Technol, 113, 1031-51.
88. Park EY, Hamanaka T, Higashiyama K, Fujikawa S. (2002). Monitoring of morphological development of the arachidonic-acid-producing filamentous microorganism Mortierella alpina. Appl Microbiol Biotechnol, 59, 706-12.
89. Park EY, Koike Y, Cai HJ, et al. (2001). Morphological diversity of Mortierella alpina: effect of consumed carbon to nitrogen ratio in flask culture. Biotechnol Bioproc Eng, 6, 161-6.
90. Park EY, Koike Y, Higashiyama K, et al. (1999). Effect of nitrogen source on mycelial morphology and arachidonic acid production in cultures of Mortierella alpina. J Biosci Bioeng, 88, 61-7.
91. Park EY, Koizumi K, Higashiyama K. (2006). Analysis of morphological relationship between micro-and macro-morphology of Mortierella species using a flow-through chamber coupled with image analysis. J Euk Microbiol, 53, 199-203.
92. Parker-Barnes JM, Das T, Bobik E, et al. (2000). Identification and characterization of an enzyme involved in the elongation of n-6 and n-3 polyunsaturated fatty acids. Proc Natl Acad Sci USA, 97, 8284-9.
93. Peng C, Huang H, Ji XJ, et al. (2010a). Effects of n-hexadecane concentration and a two-stage oxygen supply control strategy on arachidonic acid production by Mortierella alpina ME-1. Chem Eng Technol, 33, 692-7.
94. Peng C, Huang H, Ji XJ, et al. (2010b). A temperature-shift strategy for efficient arachidonic acid fermentation by Mortierella alpina in batch culture. Biochem Eng J, 53, 92-6.
95. Picataggio SK, Yadav NS, Zhu QQ. (2007). Production of polyunsaturated fatty acids in oleaginous yeasts. US Patent 7238482.
96. Pillai MG, Ahmad A, Yokochi T, et al. (2002). Biosynthesis of triacylglycerol molecular species in an oleaginous fungus, Mortierella ramanniana var. angulispora. J Biochem, 132, 121-6.
97. Qi B, Beaudoin F, Fraser T, et al. (2002). Identification of a cDNA encoding a novel C18-D9-polyunsaturated fatty acid-specific elongating activity from the docosahexaenoic acid (DHA)-producing microalga, Isochrysis galbana. FEBS Lett, 510, 159-65.
98. Qi B, Fraser T, Mugford S, et al. (2004). Production of very long chain polyunsaturated omega-3 and omega-6 fatty acids in plants. Nat Biotechnol, 22, 739-45.
99. Radwan SS, Zriek MM, Mulder JL. (1996). Distribution of arachidonic acid among lipid classes during culture aging of five Zygomycete species. Mycol Res, 100, 113-16.
100. Rajakumari S, Grillitsch K, Daum G. (2008). Synthesis and turnover of non-polar lipids in yeast. Progr Lipid Res, 47, 157-71.
101. Ratledge C. (2002). Regulation of lipid accumulation in oleaginous microorganisms. Biochem Soc Trans, 30, 1047-50.
102. Ratledge C. (2004). Fatty acid biosynthesis in microorganisms being used for single cell oil production. Biochimie, 86, 807-15.
103. Ratledge C. (2006). Microbial production of g-linolenic acid. In: Akoh CC, ed. Handbook of Functional Lipids. Boca Raton: CRC Press, 19-45.
104. Ratledge C, Streekstra H, Cohen Z, Fichtali J. (2005). Down-stream processing, extraction, and purification of single cell oils. In: Cohen Z, Ratledge C, eds. Single Cell Oils. Champaign: AOCS Press, 202-19.
105. Ratledge C, Wynn JP. (2002). The biochemistry and molecular biology of lipid accumulation in oleaginous microorganisms. Adv Appl Microbiol, 51, 1-51.
106. Ren LJ, Huang H, Xiao AH, et al. (2009). Enhanced docosahexaenoic acid production by reinforcing acetyl-CoA and NADPH supply in Schizochytrium sp. HX-308. Bioproc Biosys Eng, 32, 837-43.
107. Ryan AS, Zeller S, Nelson EB. (2010). Safety evaluation of single cell oils and the regulatory requirements for use as food ingredients. In: Cohen Z, Ratledge C, eds. Single Cell Oils: Microbial and Algal Oils. 2nd ed. Champaign: AOCS Press, 317-50.
108. Saelao S, Kanjana-Opas A, Kaewsuwan S. (2011). Optimization of biomass and arachidonic acid production by Aureispira maritima using response surface methodology. J Am Oil Chem Soc, 88, 619-29.
109. Šajbidor J, Dobroñová S, Čertík M. (1990). Arachidonic acid production by Mortierella sp. S-17 influence of C/N ratio. Biotechnol Lett, 12, 455-6.
110. Šajbidor J, Kozelouhova D, Čertík M. (1992). Influence of some metal ions on the lipid content and arachidonic acid production by Mortierella sp. Folia Microbiol, 37, 404-6.
111. Sakuradani E. (2010). Advances in the production of various polyunsaturated fatty acids through oleaginous fungus Mortierella alpina breeding. Biosci Biotechnol Biochem, 74, 908-17.
112. Sakuradani E, Ando A, Ogawa J, Shimizu S. (2009). Improved production of various polyunsaturated fatty acids through filamentous fungus Mortierella alpina breeding. Appl Microbiol Biotechnol, 84, 1-10.
113. Sakuradani E, Hirano Y, Kamada N, et al. (2004). Improvement of arachidonic acid production by mutants with lower o-3 desaturation activity derived from Mortierella alpina 1S-4. Appl Microbiol Biotechnol, 66, 243-8.
114. Sakuradani E, Shimizu S. (2009). Single cell oil production by Mortierella alpina. J Biotechnol, 144, 31-6.
115. Shaw R. (1966). The polyunsaturated fatty acids of microorganisms. Adv Lipid Res, 4, 107-74.
116. Shimizu S, Akimoto K, Kawashima H, et al. (1989). Production of dihomo-g-linolenic acid by Mortierella alpina 1S-4. J Am Oil Chem Soc, 66, 237-41.
117. Shimiziu S, Kawashima H, Shinmen Y, et al. (1988). Production of eicosapentaenoic acid by Mortierella fungi. J Am Oil Chem Soc, 65, 1455-9.
118. Shinmen Y, Shimizu S, Yamada H. (1989). Production of arachidonic acid by Mortierella fungi: selection of a potent producer and optimization of culture conditions for large-scale production. Appl Microbiol Biotechnol, 31, 11-16.
119. Singh A, Ward OP. (1997). Production of high yields of arachidonic acid in a fed-batch system by Mortierella alpina ATCC 32222. Appl Microbiol Biotechnol, 48, 1-5.
120. Sorger D, Daum G. (2003). Triacylglycerol biosynthesis in yeast. Appl Microbiol Biotechnol, 61, 289-99.
121. Stredanská S, Šajbidor J. (1993). Influence of carbon and nitrogen sources on the lipid accumulation and arachidonic acid production by Mortierella alpina. Acta Biotechnol, 13, 185-91.
122. Stredanská S, Slugeň D, Stredanský M, et al. (1993). Arachidonic acid production by Mortierella alpina grown on solid substrates. World J Microbiol Biotechnol, 9, 511-13.
123. Streekstra H. (1997). On the safety of Mortierella alpina for the production of food ingredients, such as arachidonic acid. J Biotechnol, 56, 153-65.
124. Streekstra H. (2005). Arachidonic acid: fermentative production by Mortierella fungi. In: Cohen Z, Ratledge C, eds. Single Cell Oils. Champaign: AOCS Press, 73-85.
125. Streekstra H, Brocken PJM. (2008). Preparation of microbial oil. US Patent 7470527.
126. Takeno S, Sakuradani E, Murata S, et al. (2004a). Cloning and sequencing of the ura3 and ura5 genes, and isolation and characterization of uracil auxotrophs of the fungus Mortierella alpina 1S-4. Biosci Biotechnol Biochem, 68, 277-85.
127. Takeno S, Sakuradani E, Murata S, et al. (2004b). Establishment of an overall transformation system for an oil-producing filamentous fungus, Mortierella alpina 1S-4. Appl Microbiol Biotechnol, 65, 419-25.
128. Takeno S, Sakuradani E, Murata S, et al. (2005a). Molecular evidence that the rate-limiting step for the biosynthesis of arachidonic acid in Mortierella alpina is at the level of an elongase. Lipids, 40, 25-30.
129. Takeno S, Sakuradani E, Tomi A, et al. (2005b). Improvement of the fatty acid composition of an oil-producing filamentous fungus, Mortierella alpina 1S-4, through RNA interference with D12-desaturase gene expression. Appl Environ Microbiol, 71, 5124-8.
130. Takeno S, Sakuradani E, Tomi A, et al. (2005c). Transformation of oil-producing fungus, Mortierella alpina 1S-4, using Zeocin, and application to arachidonic acid production. J Biosci Bioeng, 100, 617-22.
131. Totani N, Hyodo K, Ueda T. (2000). Minerals essential for growth of the filamentous fungus, Mortierella alpina. J Jpn Oil Chem Soc, 49, 487-93.
132. Totani N, Oba K. (1987). The filamentous fungus Mortierella alpina, high in arachidonic acid. Lipids, 22, 1060-2.
133. Totani N, Someya K, Oba K. (1992). Industrial production of arachidonic acid by Mortierella. In: Kyle DJ, Ratledge C, eds. Industrial Applications of Single Cell Oils. Champaign: AOCS Press, 52-60.
134. Totani N, Watanabe A, Oba K. (1987). An improved method of arachidonic acid production by Mortierella alpina. J Jpn Oil Chem Soc, 36, 328-31.
135. Totani N, Yamaguchi A, Yawata M, et al. (2002). The role of morphology during growth of Mortierella alpina in arachidonic acid production. J Oleo Sci, 51, 531-8.
136. Tyburczy C, Brenna ME, DeMari JA, et al. (2011). Evaluation of bioequivalency and toxicological effects of three sources of arachidonic acid (ARA) in domestic piglets. Food Chem Toxicol, 49, 2320-7.
137. Vane JR. (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature, 231, 232-5.
138. Venegas-Venegas E, Rincón-Cervera MA, Guil-Guerrero JL. (2011). Triarachidonoyl glycerol purification process. J Am Oil Chem Soc, 88, 323-8.
139. Wallis JG, Browse J. (1999). The D8-desaturase of Euglena gracilis: an alternate pathway for synthesis of 20-carbon polyunsaturated fatty acids. Arch Biochem Biophys, 365, 307-16.
140. Wang L, Chen W, Feng Y, et al. (2011a). Genome characterization of the oleaginous fungus Mortierella alpina. PLoS One, 6, e28319.
141. Wang P, Zhang L, Zheng Z, et al. (2011b). Microbial lipid production by co-fermentation with Mortierella alpina obtained by ion beam implantation. Chem Eng Technol, 34, 422-8.
142. Ward OP, Singh A. (2005). Omega-3/6 fatty acids: alternative sources of production. Proc Biochem, 40, 3627-52.
143. Warude D, Joshi K, Harsulkar A. (2006). Polyunsaturated fatty acids: biotechnology. Crit Rev Biotechnol, 26, 83-93.
144. Wynn JP, Hamid AA, Li Y, et al. (2001). Biochemical events leading to the diversion of carbon into storage lipids in the oleaginous fungi Mucor circinelloides and Mortierella alpina. Microbiology, 147, 2857-64.
145. Wynn JP, Hamid AA, Ratledge C. (1999). The role of malic enzyme in the regulation of lipid accumulation in filamentous fungi. Microbiology, 145, 1911-17.
146. Wynn JP, Ratledge C. (2000). Evidence that the rate-limiting step for the biosynthesis of arachidonic acid in Mortierella alpina is at the level of the 18: 3 to 20: 3 elongase. Microbiology, 146, 2325-31.
147. Wynn JP, Ratledge C. (2005). Oils from microorganisms. In: Shahidi F, ed. Bailey's Industrial Oil and Fat Products. 6th ed. New York: John Wiley & Sons, Inc, 121-53.
148. Yamada H, Shimizu S, Shinmen Y. (1987). Production of arachidonic acid by Mortierella elongata 1S-5. Agric Biol Chem, 51, 785-90.
149. Yao J, Wang J, Wang X, et al. (2000). Breeding of arachidonic acid producing strain by ion implantation. Chin J Biotechnol, 16, 478-81.
150. You JY, Peng C, Liu X, et al. (2011). Enzymatic hydrolysis and extraction of arachidonic acid rich lipids from Mortierella alpina. Bioresour Technol, 102, 6088-94.
151. Yu LJ, Qin WM, Lan WZ, et al. (2003). Improved arachidonic acids production from the fungus Mortierella alpina by glutamate supplementation. Bioresour Technol, 88, 265-8.
152. Yuan C, Wang J, Shang Y, et al. (2002). Production of arachidonic acid by Mortierella alpina I49-N18. Food Technol Biotechnol, 40, 311-15.
153. Zeng Y, Ji XJ, Chang SM, et al. (2012). Improving arachidonic acid accumulation in Mortierella alpina through B-group vitamin addition. Bioproc Biosyst Eng, 35, 683-8.
154. Zeng Y, Ji XJ, Lian M, et al. (2011). Development of a temperature shift strategy for efficient docosahexaenoic acid production by a marine fungoid protist, Schizochytrium sp. HX-308. Appl Biochem Biotechnol, 87, 1649-56.
155. Zhang CW, Cohen Z, Khozin-Goldberg I, et al. (2002). Characterization of growth and arachidonic acid production of Parietochloris incisa comb. nov (Trebouxiophyceae, Chlorophyta). J Appl Phycol, 14, 453-60.
156. Zhang Y, Adams IP, Ratledge C. (2007). Malic enzyme: the controlling activity for lipid production? Overexpression of malic enzyme in Mucor circinelloides leads to a 2.5-fold increase in lipid accumulation. Microbiology, 153, 2013-25.
157. Zhao M, Dai C, Guan X, Tao J. (2009). Genome shuffling amplifies the carbon source spectrum and improves arachidonic acid production in Diasporangium sp. Enzyme Microb Technol, 45, 419-25.
158. Zhou PP, Yu LJ, Li W, et al. (2005). The effect of YAG laser on Mortierella alpina producing arachiclonic acid. Acta Las Biol Sin, 14, 129-33.
159. Zhou PP, Yu LJ, Zhu M, et al. (2000). Strain improvement of arachidonic acid-producing by protoplast mutagenesis. J Huazhong Univ Sci Technol, 28, 105-10.
160. Zhu M, Yu LJ, Li W, et al. (2006). Optimization of arachidonic acid production by fed-batch culture of Mortierella alpina based on dynamic analysis. Enzyme Microb Technol, 38, 735-40.
161. Zhu M, Yu LJ, Liu Z, Xu HB. (2004). Isolating Mortierella alpina strains of high yield of arachidonic acid. Lett Appl Microbiol, 39, 332-5.
162. Zhu M, Yu LJ, Wu YX. (2003). An inexpensive medium for production of arachidonic acid by Mortierella alpina. J Ind Microbiol Biotechnol, 30, 75-9.
163. Zhu M, Zhou PP, Yu LJ. (2002). Extraction of lipids from Mortierella alpina and enrichment of arachidonic acid from the fungal lipids. Bioresour Technol, 84, 93-5.