Skip to main content
Log in

Biotechnological production and applications of the ω-3 polyunsaturated fatty acid docosahexaenoic acid

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid composed of 22 carbon atoms and six double bonds. Because the first double bond, as counted from the methyl terminus, is at position three, DHA belongs to the so-called ω-3 group. In recent years, DHA has attracted much attention because of its beneficial effect on human health. At present, fish oil is the major source of DHA, but alternatively it may be produced by use of microorganisms. Marine microorganisms may contain large quantities of DHA and are considered a potential source of this important fatty acid. Some of these organisms can be grown heterotrophically on organic substrates without light. These processes can be well controlled and DHA with constant quality can be produced all year round. This paper reviews recent advances in the biotechnological production of DHA by marine microorganisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ackman RG, Jangaard PM, Hoyle RJ, Brockerhoff H (1964) Origin of marine fatty acids. Analysis of the fatty acids produced by the diatom Skeletonema costatum. J Fish Res Board Can 21:747–756

    CAS  Google Scholar 

  • Bajpai P, Bapai PK, Ward OP (1991) Production of docosahexaenoic acid by Traustochytrium aureum. Appl Microbiol Biotechnol 35:706–710

    CAS  Google Scholar 

  • Barclay WR (1991) Process for the heterotrophic production of products with high concentrations of omega-3 highly unsaturated fatty acids. World patent WO91/07498

  • Barclay WR, Meager KM, Abril JR (1994) Heterotrophic production of long chain omega-3 fatty acids utilizing algae and algae-like microorganisms. J Appl Phycol 6:123–129

    CAS  Google Scholar 

  • Beach DH, Holz GG (1973) Environmental influences on the docosahexaenoate content of the triacylglycerols and phosphatidylcholine of a heterotrophic, marine dinoflagellate, Crythecodinium cohnii. Biochim Biophys Acta 316:56

    Article  CAS  PubMed  Google Scholar 

  • Bowles RD, Hunt AE, Bremer GB, Duchars MG, Eaton RA (1999) Long-chain n-3 polyunsaturated fatty acid production by members of the marine protistan group of the traustochytrids: screening of isolates and optimisation of docosahexaenoic acid production. J Biotechnol 70:193–202

    Article  CAS  Google Scholar 

  • British Nutrition Foundation (1992) Unsaturated fatty acids, nutritional and physiological significance. The report of the British Nutrition Foundation’s task force. Chapman and Hall, London

  • Chen F (1996) High cell density culture of microalgae in heterotrophic growth. Trends Biotechnol 14:421–426

    Article  CAS  Google Scholar 

  • Cohen Z, Norman HA, Heimer YM (1995) Microalgae as a source of omega-3 fatty acids. World Rev Nutr Diet 77:1–31

    CAS  PubMed  Google Scholar 

  • Crawford P (1987) The requirements of long-chain n-6 and n-3 fatty acids for the brain. In: Lands WEM (ed) Short course in polyunsaturated fatty acids and eicosanoids. (Proceedings of the AOCS Conference) Proc Am Oil Chem Soc 1987:270–295

  • Crawford MA, Costeloe K, Ghebremeskel K, Phlactos A, Skirvin L, Stacey F (1997) Are deficits of arachidonic and docosahexaenoic acids responsible for the neural and vascular complications of pre-term babies? Am J Clin Nutr 66:1032S–1041S

    CAS  PubMed  Google Scholar 

  • Das UN, Fams MD (2003) Long-chain polyunsaturated fatty acids in the growth and development of the brain and memory. Nutrition 19:62–65

    Article  CAS  PubMed  Google Scholar 

  • Davies RJ (1992) Scale-up of yeast oil technology. In: Kyle DJ, Ratledge C (eds) Industrial applications of single cell oils. American Oil Chemists’ Society, Champaign, Ill., p. 196–218

  • Fan KW, Chen F, Jones EBG, Vrijmoed LLP (2001) Eicosapentaenoic and docosahexaenoic acids production by okara utilizing potential of traustochytrids. J Ind Microbiol Chem 27:199–2002

    Article  CAS  Google Scholar 

  • FAO/WHO Expert Committee (1994) Food and nutrition paper 57. FAO, Rome

  • Gawrisch K, Eldho N (2002) Docosahexaenoic vs docosapentaenoic acid: the difference that the loss of a single double bond makes. Fifth Congress of the International Society for the Study of Fatty Acids and Lipids, Montreal

    Google Scholar 

  • Gerbling H, Axiotis S, Douce R (1994) A new acyl-CoA synthetase, located in higher plant cytosol. J Plant Physiol 143:561–564

    CAS  Google Scholar 

  • Gill I, Valivety R (1997) Polyunsaturated fatty acids, part 1: occurrence, biological activities and applications. Trends Biotechnol 15:401–409

    Article  CAS  PubMed  Google Scholar 

  • Giusto NM, Pasquare SJ, Salvador PI, Roque MG (2000) Lipid metabolism in vertebrate retinal rod outer segments. Prog Lipid Res 39:315–391

    Article  CAS  PubMed  Google Scholar 

  • Gunstone FD (1996) Fatty acid and lipid chemistry. Blackie Academic, London

  • Gunstone FD (2001) Basic oleochemicals, oleochemical products and new industrial oils. In: Gunstone FD, Hamilton RJ (eds) Oleochemical manufacture and application. Sheffield Academic Press, Sheffield, pp 1–22

  • Gunstone FD, Harwood JL, Padley FB (1994) The lipid handbook. Chapman and Hall, London

  • Harrington GW, Holz GG (1968) The monoenoic and docosahexaenoic fatty acids of a heterotrophic dinoflagellate. Biochim Biophys Acta 164:137–139

    CAS  PubMed  Google Scholar 

  • Horrocks LA, Yeo YK (1999) Health benefits of docosahexaenoic acid (DHA). Pharmacol Res 40:211–225

    Article  PubMed  Google Scholar 

  • Horrocks LA, Young KY (1999) Docosahexaenoic acid-enriched foods: production and effects on blood lipids. Lipids 34:S313

    CAS  PubMed  Google Scholar 

  • Huang J, Hachida K, Yokochi T, Kawamoto S, Shigeta S, Ono K, Osamu S (2001) Profile of polyunsaturated fatty acids produced by Thraustochytrium sp. KK17-3. J Am Oil Chem Soc 78:605–610

    CAS  Google Scholar 

  • Huisman M, Beusekom CM van, Lanting CI, Nijeboer HJ, Muskiet FAJ, Boersma ER (1996) Triglycerides, fatty acids, sterols, mono- and disaccharides and sugar alcohols in human milk and current types of infant formula milk. Eur J Clin Nutr 50:255–260

    CAS  PubMed  Google Scholar 

  • Kang JX, Leaf A (1996) The cardiac antiarrhythmic effects of polyunsaturated fatty acid. Lipids 31:S41–S44

    CAS  PubMed  Google Scholar 

  • Kendrick A, Ratledge C (1992) Lipids of selected molds grown for production of n-3 and n-6 polyunsaturated fatty acids. Lipids 27:15–20

    CAS  PubMed  Google Scholar 

  • Kispal G, Cseko J, Alkonyi I, Sandor A (1991) Isolation and characterisation of carnitine acetyltransferase from Saccharomyces cerevisiae. Biochim Biophys Acta 1085:217–222

    Article  CAS  PubMed  Google Scholar 

  • Klein HP, Jahnke L (1971) Variations in the localisation of acetyl-coenzyme A synthetase in aerobic yeast cells. J Bacteriol 106:596–602

    CAS  PubMed  Google Scholar 

  • Knudsen CT, Immerdal L, Grunnet N, Quistorff B (1992) Peritonal zonation of the cytosolic acetyl-CoA synthetase of male rat liver. Eur J Biochem 204:359–362

    CAS  PubMed  Google Scholar 

  • Kromann N, Green A (1980) Epidemiological studies in the Upernavik district, Greenland. Incidence of some chronic diseases 1950–1974. Acta Med Scand 208:401–406

    CAS  PubMed  Google Scholar 

  • Kyle DJ (1994) Microbial oil mixtures and uses thereof, Martek Corp. US patent 5,374,657

  • Kyle DJ (1996) Production and use of a single cell oil which is highly enriched in docosahexaenoic acid. Lipid Technol 8:107–110

    Google Scholar 

  • Kyle DJ (1997) Production and use of a single cell oil highly enriched in arachidonic acid. Lipid Technol 9:116–121

    CAS  Google Scholar 

  • Kyle DJ, Reeb SE, Sicotte VJ (1995) Infant formula and baby food containing docosahexaenoic acid obtained from dinoflagellates, Martek Biosciences Corp. US patent 5,397,591

  • Kyle DJ, Reeb SE, Sicotte VJ (1998) Docosahexaenoic acid, methods for its production and compounds containing the same, Martek Corp. European patent 0515460B1

  • Meireles LA, Guedes AC, Malcata FX (2002) Increase of the yields of eicosapentaenoic and docosahexaenoic acids by the microalgae Pavlova lutheri folllowing random mutagenesis. Biotechnol Bioeng 81:50–55

    Article  Google Scholar 

  • 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 synthetases in both prokaryotes and eukaryotes. Science 293:290–293

    Article  CAS  PubMed  Google Scholar 

  • Molina Grima E, Sánchez Pérez JA, Garciá Camacho F,Garciá Sánchez JL, López Alonso D (1993) n-3 PUFA productivity in chemostat cultures of microalgae. Appl Microbiol Biotechnol 38:599–605

    Google Scholar 

  • Mukherjee KD (1999) Production and use of microbial oils. INFORM 10:308–313

    Google Scholar 

  • Nakahara T, Yokocki T, Kamisaka Y, Suzuki S (1992) γ-Linolenic acid from genus Mortierella. In: Kyle DJ, Ratledge C (eds) Industrial applications of single cell oils. American Oil Chemists’ Society, Champaign, Ill., pp 61–97

  • Nakahara T, Yokochi T, Higashihara T, Tanaka S, Yagishi Y, Honda D (1996) Production of docosahexaenoic and docosapentaenoic acid by Schizochytrium sp. isolated from Yap islands. J Am Oil Chem Soc 73:1421–1426

    CAS  Google Scholar 

  • Nettleton JA (1993) Are n-3 fatty acids essential nutrients for fetal and infant development? J Am Diet Assoc 93:58–64

    CAS  PubMed  Google Scholar 

  • Newton IS (1998) Long-chain polyunsaturated fatty acids—the new frontier in nutrition. Lipid Technol 10:77–81

    CAS  Google Scholar 

  • Nordøy A, Marchioli R, Arnesen H, Videbaek J (2001) n-3 polyunsaturated fatty acids and cardiovascular diseases. Lipids 36:S127–S129

    PubMed  Google Scholar 

  • Preez JC du, Immelman M, Kock JFL, Kilian SG (1995) Production of γ-linolenic acid by Mucor circinelloides and Mucor rouxii with acetic acid as carbon substrate. Biotechnol Lett 17:933–938

    Google Scholar 

  • Pulz O (2001) Photobioreactors: production systems for phototrophic microorganisms. Appl Microbiol Biotechnol 57:287–293

    Article  CAS  PubMed  Google Scholar 

  • Ratledge C (2001) Microorganisms as sources of polyunsaturated fatty acids. In: Gunstone FD (ed) Structured and modified lipids. Dekker, New York, pp 351–399

  • Ratledge C, Evans CT (1989) Lipids and their metabolism. In: Rose AH, Harrison JS (eds) The yeasts, vol 3, 2nd edn. Academic Press, London, pp 367–455

  • Ratledge C, Kanagachandran K, Anderson AJ, Grantham DJ, Stephenson JM (2001a) Production of docosahexaenoic acid by Crypthecodinium cohnii grown in a pH-auxostat culture with acetic acid as principal carbon source. Lipids 36:1241–1246

    CAS  PubMed  Google Scholar 

  • Ratledge C, Anderson AJ, Kanagachandran K, Grantham DJ, Stepherson JC, Swaaf ME de, Sijtsma L (2001b). Culture of Crypthecodinium cohnii for the synthesis of a polyunsaturated fatty acid. Patent WO 01/04338

  • Ratwan SS (1991) Sources of C20-polyunsaturated fatty acids for biotechnological use. Appl Microbiol Biotechnol 35:421–430

    Google Scholar 

  • Rodríguez C, Pérez JA, Badía P, Izquierdo MS, Fernández-Palacios H, Hernández L (1998) The n-3 highly unsaturated fatty acids requirements of gilthead seabream (Sparus aurata L.) larvae when using an appropriate DHA/EPA ratio in the diet. Aquaculture 169:9–23

    Article  Google Scholar 

  • Schmidt EB, Christensen JH, Aardestrup I, Madsen T, Riahi S, Hansen VE, Skou HA (2001) Marine n-3 fatty acids: basic features and background. Lipids 36:S65–S68

    CAS  PubMed  Google Scholar 

  • Servel MO, Claire C, Derrien A, Coiffard L, Roeck-Holtzhauer Y de (1994) Fatty acid composition of some marine microalgae. Phytochemistry 36:691–693

    Article  Google Scholar 

  • Sijtsma L, Springer J, Meesters PAEP, Swaaf ME de, Eggink G (1998) Recent advances in fatty acid synthesis in oleaginous yeasts and microalgae. Recent Res Dev Microbiol 2:219–232

    CAS  Google Scholar 

  • Singh A, Ward OP (1996) Production of high yields of docosahexaenoic acid by Traustochytrium roseum ATCC 20810. J Ind Microbiol 16:370–373

    CAS  Google Scholar 

  • Storey KB, Bailey E (1978) Intracellular distribution of enzymes associated with lipogenesis and gluconeogenesis in fat body of the adult cockroach, Periplaneta. Insect Biochem 8:125–131

    Article  CAS  Google Scholar 

  • Swaaf ME de (2003) Docosahexaenoic acid production by the marine alga Crypthecodinium cohnii. PhD thesis, Technical University Delft, Delft

  • Swaaf ME de, Rijk TC de, Eggink G, Sijtsma L (1999) Optimisation of docosahexaenoic acid production in batch cultivations by Crypthecodimium cohnii. J Biotechnol 70:185–192

    Google Scholar 

  • Swaaf ME de, Grobben GJ, Eggink G, Rijk TC de, Meer P van der, Sijtsma L (2001) Characterisation of extracellular polysaccharides produced by Crypthecodinium cohnii. Appl Microbiol Biotechnol 57:395–400

    PubMed  Google Scholar 

  • Swaaf ME de, Sijtsma L, Pronk JT (2003a) High-cell-density fed-batch cultivation of the docosahexaenoic-acid producing marine alga Crypthecodinium cohnii. Biotechnol Bioeng 81:666–672

    Article  PubMed  Google Scholar 

  • Swaaf ME de, Pronk JT, Sijtsma L (2003b) Fed-batch cultivation of the docosahexaenoic acid producing marine alga Crypthecodinium cohnii on ethanol. Appl Microbiol Biotechnol 61:40–43

    PubMed  Google Scholar 

  • Swaaf ME de, Rijk TC de, Meer P van der, Eggink G, Sijtsma L (2003c) Analysis of docosahexaenoic acid biosynthesis in Crypthecodinium cohnii by 13C labelling and desaturase inhibitor experiments. J Biotechnol 103:21–29

    PubMed  Google Scholar 

  • Tuominen TR, Esmark M (2003) Food for thought: the use of marine resources in fish feed. (WWF Report 02/03) WWF, Oslo

    Google Scholar 

  • Vazhappilly R, Chen F (1998) Heterotrophic production of potential omega-3 polyunsaturated fatty acids by microalgae and algae-like microorganisms. Bot Mar 41:553–558

    CAS  Google Scholar 

  • Viso AC, Marty JC (1993) Fatty acids from 28 marine microalgae. Phytochemistry 34:1521–1533

    CAS  Google Scholar 

  • Yaguchi T, Tanaka S, Yokochi T, Nakahara T, Yaguchi T (1997) Production of high yields of docodahexaenoic acids by Schizochytrium sp. strain SR21. J Am Oil Chem Soc 74:1431–1434

    CAS  Google Scholar 

  • Yamamura R, Shimomura Y (1997) Industrial high-performance liquid chromatography purification of docosahexaenoic acid ethyl ester and docosapentaenoic acid ethyl ester from single-cell oil. J Am Oil Chem Soc 74:1435–1440

    CAS  Google Scholar 

  • Yokochi T, Honda D, Higashihara T, Nakahara T (1998) Optimisation of docosahexaenoic acid production by Schizochytrium limacinum SR21. Appl Microbiol Biotechnol 49:72–76

    CAS  Google Scholar 

  • Zeller S, Barclay W, Elswyk M van, Abril R, Sander W (2002) The impact of dietary docodahexaenoic acid and docosapentaenoic acid from Schizochytrium sp. on rat and swine tissue. Fifth Congress of the International Society for the Study of Fatty Acids and Lipids, Montreal

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Sijtsma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sijtsma, L., de Swaaf, M.E. Biotechnological production and applications of the ω-3 polyunsaturated fatty acid docosahexaenoic acid. Appl Microbiol Biotechnol 64, 146–153 (2004). https://doi.org/10.1007/s00253-003-1525-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-003-1525-y

Keywords

Navigation