Abstract
Microalgae have the ability to convert inorganic compounds into organic compounds. When they are cultured in the presence of stable (non-radioactive) isotopes (i.e.13CO2,15NO −3 ,2H2O) their biomass becomes labeled with the stable isotopes, and a variety of stable isotopically-labeled compounds can be extracted and purified from that biomass.
Two applications for stable isotopically-labeled compounds are as cell culture nutrients and as breath test diagnostics. Bacteria that are cultured with labeled nutrients will produce bacterial products that are labeled with stable isotopes. The presence of these isotopes in the bacterial products, along with recent developments in NMR technology, greatly reduces the time and effort required to determine the three-dimensional structure of macromolecules and the interaction of proteins with ligands. As breath test diagnostics, compounds labeled with13C are used to measure the metabolism of particular organs and thus diagnose various disease conditions. These tests are based on the principle that a particular compound is metabolized primarily by a single organ, and when that compound is labeled with13C, the appearance of13CO2 in exhaled breath provides information about the metabolic activity of the target organ. Tests of this type are simple to perform, non-invasive, and less expensive than many conventional diagnostic procedures.
The commercialization of stable isotopically labeled compounds requires that these compounds be produced in a cost-effective manner. Our approach is to identify microalgal overproducers of the desired compounds, maximize the product content of those organisms, and purify the resulting products.
Similar content being viewed by others
References
Armitige I (1990) NMR methods for elucidating macromolecular-ligand interactions: An approach to drug design. Biochem. Pharmacol. 40: 1.
Behrens PW, Bingham SE, Hoeksema SD, Cohoon DL, Cox JC (1989) Studies on the incorporation of CO2 into starch byChlorella vulgaris. J. appl. Phycol. 1: 123–130.
Behrens PW, Marsho TV, Radmer RJ (1982) Photosynthetic oxygen exchange kinetics in isolated soybean cells. Plant Physiol. 70: 179–185.
Brand LE, Guillard RRL (1981) The effects of continuous light and light intensity on the reproduction rates of twenty-two species of marine phytoplankton. J. exp. mar. Biol. Ecol. 50: 119–132.
Calvin M, Massini P (1952) The path of carbon in photosynthesis. Experientia 8: 445–457.
Caspary WF, Schaffer J (1978)14C-d-galactose breath test for the evaluation of liver function in patients with chronic liver disease. Digestion 17: 410–418.
Chaplin MF, Kennedy JF (1986) Carbohydrate Analysis: A Practical Approach. IRL Press, Oxford.
Chorney W, Scully NJ, Crespi HL, Katz JJ (1960) The growth of algae in deuterium oxide. Biochim. Biophys. Acta 37: 280–287.
Cohen Z (1986) Products from microalgae. In Richmond A (ed.) Handbook of Microalgal Mass Culture. CRC Press, Boca Raton: 421–454.
Crespi HL, Archer SM, Katz JJ (1959) Culture of algae and other microorganisms in deuterium oxide. Nature 184: 729–730.
Fesik SW, Gampe RT, Holzman TF, Egan DA, Edalji R, Luly JR, Simmer R, Helfrich R, Kishore V, Rich DH (1990) Isotope-edited NMR of cyclosporin A bound to cyclophilin: Evidence for a trans 9, 10 amide bond. Science 250: 1406–1409.
Graham DY, Klein PD, Evans DJ, Evans DG, Alpert LC, Opekun AR, Boutton TW (1987)Campylobacter pylori detected noninvasively by the13C-urea breath test. Lancet 1: 1174–1177.
Hofmann AF, Lauterburg BH (1977) Breath tests with isotopes of carbon: progress and potential. J. lab. clin. med. 90: 405–411.
Hsu VL, Heald SL, Harding MW, Handschumacher RE, Armitage IM (1990) Structural elements pertinent to the interaction of cyclosporin A with its specific receptor protein, cyclophilin. Biochem. Pharmacol. 40: 131–140.
Ikura M, Marion D, Kay LE, Shih H, Krinks M, Klee CB, Bax A (1990) Heteronuclear 3D NMR and isotopic labeling of calmodulin. Biochem. Pharmacol. 40: 153–160.
Kay LE, Clore GM, Bax A, Gronenborn AM (1990) Four dimensional heteronuclear triple-resonance NMR spectroscopy of interleukin-1B in solution. Science 249: 411–414.
King CE, Toskes PP (1983) The use of breath tests in the study of malabsorption. Clin. Gastroent. 12: 591–610.
LeMaster DM, Richards FM (1988) NMR sequential assignment ofEscherischia coli thioredoxin utilizing random fractional deuteration. Biochemistry 27: 142–150.
Moses V, Holm-Hansen O, Calvin M (1958) Responses ofChlorella to a deuterium environment. Biochim. Biophys. Acta 28: 62–70.
Oh BH, Westler WH, Darba P, Markley JL (1988) Protein carbon-13 spin systems by a single two dimensional nuclear magnetic resonance experiment. Science 240: 908–911.
Piorreck M, Baasch K-H, Pohl P (1984) Biomass production, total protein, chlorophyll, lipids and fatty acids of fresh water green and blue green algae under different nitrogen regimes. Phytochemistry 23: 207–216.
Piorreck M, Pohl P (1984) Formation of biomass, total protein, chlorophylls, lipids and fatty acids in green and blue green algae during one growth phase. Phytochemistry 23: 217–223.
Pohl P, Passig T, Wagner H (1971) On the effect of inorganic nitrogen content in the nutrient solution on the biosynthesis of fatty acids in green algae. Phytochemistry 10: 1505–1513.
Radmer RJ, Behrens PW, Arnett KL (1987) An analysis of the continuous algal culture system. Biotechnol. Bioengin. 24: 488–492.
Richardson B, Orcutt DM, Schwetner HA, Martinez CL, Wickline HE (1969) Effects of nitrogen limitation on the growth and composition of unicellular algae in continuous culture. Appl. Microbiol. 18: 245–250.
Shifrin NS, Chisholm SW (1981) Phytoplankton lipids: Interspecific differences and effects of nitrate, silicate and light-dark cycles. J. Phycol. 17: 374–384.
Shreeve WW, Shoop JD, Ott DG, McInteer BB (1976) Test for alcoholic cirrhosis by conversion of1C- or13C-galactose to expired CO2. Gastroenterology 71: 98–101.
Sukenik A, Carmeli Y, Berner T (1989) Regulation of fatty acid composition by irradiance level in the eustigmatophyteNannochloropsis sp. J. Phycol. 25: 686–692.
Taecker RG, Crespi HL, Daboll HF, Katz JJ (1971) Deep tank culture of blue-green algae in H2O and D2O. Biotechnol. Bioeng. 13: 779–793.
Tornabene TG, Holzer G, Lien S, Burris N (1983) Lipid composition of the nitrogen starved green algaNeochloris oleoabundans. Enzyme Microb. Technol. 5: 435–440.
Turner JM, Lawrence S, Fellows IW, Johnson I, Hill PG, Holmes GKT (1987)14C-triolein absorption: a useful test in the diagnosis of malabsorption. Gut 28: 694–700.
Walker JR, Syrett PJ (1959) Effect of heavy water on the growth ofChlorella vulgaris. Nature 183: 1193–1194.
Williams AJ, Morse AT, Stuart RS (1966) Production of green algae in deuterium oxide. Can. J. Microbiol. 12: 1167–1173.
Wright PE, Dyson HJ, Lerner RA, Riechmann L, Tsang P (1990) Antigen-antibody interactions: An NMR approach. Biochem. Pharmacol. 40: 83–88.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Behrens, P.W., Sicotte, V.J. & Delente, J. Microalgae as a source of stable isotopically labeled compounds. J Appl Phycol 6, 113–121 (1994). https://doi.org/10.1007/BF02186065
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02186065