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Algae acquire vitamin B12 through a symbiotic relationship with bacteria

Nature volume 438, pages 9093 (03 November 2005) | Download Citation



Vitamin B12 (cobalamin) was identified nearly 80 years ago as the anti-pernicious anaemia factor in liver1, and its importance in human health and disease has resulted in much work on its uptake2, cellular transport3 and utilization4. Plants do not contain cobalamin because they have no cobalamin-dependent enzymes. Deficiencies are therefore common in strict vegetarians5, and in the elderly, who are susceptible to an autoimmune disorder that prevents its efficient uptake6. In contrast, many algae are rich in vitamin B12, with some species, such as Porphyra yezoensis (Nori), containing as much cobalamin as liver7. Despite this, the role of the cofactor in algal metabolism remains unknown, as does the source of the vitamin for these organisms. A survey of 326 algal species revealed that 171 species require exogenous vitamin B12 for growth, implying that more than half of the algal kingdom are cobalamin auxotrophs. Here we show that the role of vitamin B12 in algal metabolism is primarily as a cofactor for vitamin B12-dependent methionine synthase, and that cobalamin auxotrophy has arisen numerous times throughout evolution, probably owing to the loss of the vitamin B12-independent form of the enzyme. The source of cobalamin seems to be bacteria, indicating an important and unsuspected symbiosis.

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  1. 1.

    & Treatment of pernicious anemia by a special diet. 1926. Yale J. Bio. Med. 74, 341–353 (2001)

  2. 2.

    , & Cellular import of cobalamin (Vitamin B12). J. Nutr. 129, 1761–1764 (1999)

  3. 3.

    & Absorption and transport of cobalamin (vitamin B12). Annu. Rev. Nutr. 2, 343–369 (1982)

  4. 4.

    & The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes. Annu. Rev. Biochem. 72, 209–247 (2003)

  5. 5.

    et al. Characterization of a vitamin B12 compound in the edible purple laver, Porphyra yezoensis. Biosci. Biotech. Biochem. 64, 2712–2715 (2000)

  6. 6.

    & Vitamin B12 deficiency as a worldwide problem. Annu. Rev. Nutr. 24, 299–326 (2004)

  7. 7.

    Vitamins in algae. Bull. Jap. Soc. Sci. Fish. 29, 713–731 (1963)

  8. 8.

    , , & The biosynthesis of adenosylcobalamin (Vitamin B12). Nat. Prod. Rep. 19, 390–412 (2002)

  9. 9.

    & Vitamin production and utilization by phytoplankton in mixed culture. J. Phycol. 6, 393–400 (1970)

  10. 10.

    & in Algal Physiology and Biochemistry (ed. Stewart, W. D. P.) 741 (Blackwell, Oxford, 1974)

  11. 11.

    et al. Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature 428, 653–657 (2004)

  12. 12.

    et al. The genome of the diatom Thalassiosira pseudonana: ecology, evolution, and metabolism. Science 306, 79–86 (2004)

  13. 13.

    , , & Vitamin B12 metabolism in a photosynthesizing green alga, Chlamydomonas reinhardtii. Biochim. Biophys. Acta 1075, 36–41 (1991)

  14. 14.

    , , , & Comparison of cobalamin-independent and cobalamin-dependent methionine synthases from Escherichia coli: two solutions to the same chemical problem. Biochemistry 31, 6045–6056 (1992)

  15. 15.

    & Folate/vitamin B12 inter-relationships. Essays Biochem. 28, 63–72 (1994)

  16. 16.

    et al. Hyperhomocysteinemia, low folate and vitamin B12 concentrations, and methylene tetrahydrofolate reductase mutation in cerebral venous thrombosis. Stroke 35, 1790–1794 (2004)

  17. 17.

    in Chrysophytes: Aspects and Problems (eds Kristiansen, J. & Andersen, R. A.) 185–196 (Cambridge Univ. Press, Cambridge, 1986)

  18. 18.

    The ecology of the plankton off La Jolla, California in the period April through September, 1967. II. Vitamin B12, thiamine and biotin. Bull. Sci. Inst. Ocean 17, 23–30 (1970)

  19. 19.

    , , , & Purification and characterization of methylmalonyl-CoA mutase from a photosynthetic coccolithophorid alga, Pleurochrysis carterae. Comp. Biochem. Physiol. B 138, 163–167 (2004)

  20. 20.

    Ribonucleotide reductase from Euglena gracilis. A 5′-deoxyadenoslycobalamin-dependent enzyme. J. Biol. Chem. 249, 4428–4434 (1974)

  21. 21.

    , , , & Chlorophyll d in an epiphytic cyanobacterium of red algae. Science 303, 1633 (2004)

  22. 22.

    , , & Primary production of the biosphere: integrating terrestrial and oceanic components. Science 281, 237–240 (1998)

  23. 23.

    Acquisition and utilization of transition metal ions by marine organisms. Science 281, 207–210 (1998)

  24. 24.

    , & Oligotrophic bacteria enhance algal growth under iron-deficient conditions. Appl. Environ. Microbiol. 61, 2439–2441 (1995)

  25. 25.

    Synthesis of bile pigments in plants. Formation of carbon monoxide and phycocyanobilin in wild-type and mutant strains of the alga, Cyanidium caldarium. Biochemistry 11, 4235–4242 (1972)

  26. 26.

    et al. Salmonella typhimurium cobalamin (vitamin B12) biosynthetic genes: functional studies in S. typhimurium and Escherichia coli. J. Bacteriol. 178, 753–767 (1996)

  27. 27.

    Nucleic Acid Techniques in Bacterial Systematics (eds Stackebrandt, E. & Goodfellow, M.) 115 (John Wiley and Sons, New York, 1991)

  28. 28.

    et al. A phylogenetic assessment of the eukaryotic light-harvesting antenna proteins, with implications for plastid evolution. J. Mol. Evol. 48, 59–68 (1999)

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We thank C. Howe, S. Purton, S. Beale and D. Vernon for the donation of algal strains, the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK for the award of an earmarked studentship to M.T.C., the European Union Viteomics Research Training Network for funding and for providing a forum for discussions, and Queen Mary University of London for providing a studentship to A.D.L. Author Contributions This work is the result of a collaboration between the laboratories of M.J.W. and A.G.S. through the joint earmarked studentship for M.T.C.

Author information


  1. Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, UK

    • Martin T. Croft
    •  & Alison G. Smith
  2. Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK

    • Andrew D. Lawrence
    • , Evelyne Raux-Deery
    •  & Martin J. Warren


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Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Alison G. Smith.

Supplementary information

Word documents

  1. 1.

    Supplementary Methods

    This file contains additional details of methods used in this study.

PDF files

  1. 1.

    Supplementary Table 1

    A list of all the algae in the survey.

  2. 2.

    Supplementary Figure 1

    This figure shows growth data for the red alga Porphyridium purpureum.

  3. 3.

    Supplementary Figure 2

    This figure shows growth data for the dinoflagellate Amphidinium operculatum.

  4. 4.

    Supplementary Figure 3

    This figure shows growth data for the Euglenoid Euglena gracilis.

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