Process Strategies to Enhance the Production of 5-Aminolevulinic Acid with Recombinant E. coli

  • LEE , DAE-HEE (Department of Food and Biotechnology, School of Life Sciences and Biotechnology, Korea University) ;
  • JUN, WOO-JIN (Department of Food and Nutrition, Chonnam National University) ;
  • YOON, JEONG-WEON (Department of Bioscience and Biotechnology, Suwon University) ;
  • CHO, HONG-YON (Department of Food and Biotechnology, School of Life Sciences and Biotechnology, Korea University) ;
  • HONG, BUM-SHIK (Department of Food and Biotechnology, School of Life Sciences and Biotechnology, Korea University)
  • Published : 2004.12.01

Abstract

The extracellular production of 5-aminolevulinic acid (ALA) by recombinant E. coli BL21 harboring a fusion gene hemA was investigated in a fermenter. For this purpose, the effects of various physiological factors, such as isopropylthio­$\beta$-D-galactopyranoside (IPTG) concentrations and the time of induction, on enzyme activity were studied. Optimum concentrations of glycine and succinic acid were found to be 30 mM and 90 mM, respectively. When the cells were permitted to grow for 2 h prior to the addition of 0.1 mM IPTG, the activity of ALA synthase was higher than when IPTG was initially added. A 36-fold increase in the activity was observed with only 0.1 mM IPTG added. The pH of the medium also influenced the ALA synthase activity with the maximal activity occurring at pH 6.5. In recombinant E. coli extracts, the repeated addition of glycine and D-glucose increased the production of ALA and the inhibited intracellular ALA dehydratase activity, with up to 32 mM ALA being produced in the cultivation.

Keywords

References

  1. Baca-DeLancey, R. R., M. M. T. South, X. Doing, and P. N. Rather. 1999. Escherichia coli genes regulated by cell-to-cell signaling. Proc. Natl. Acad. Sci. USA 96: 4610-4614
  2. Beale, S. I. 1978. $\delta$-Aminolevulinic acid in plants: Its biosynthesis, regulation, and role in plastid development. Ann. Rev. Physiol. 29: 95-120 https://doi.org/10.1146/annurev.pp.29.060178.000523
  3. Burnham, B. F. 1970.TEX>$\delta$-Aminolevulinic acid synthase (Rhodopseudomonas sphaeroides). Methods Enzymol. 17A: 195-200
  4. Butler, A. R. and S. George. 1992. The nonenzymatic cyclic dimerisation of 5-aminolevulinic acid. Tetrahedron 48: 7879-7886
  5. Cho, Y. S., L. D. Park, Y. W. Kim, H. Hwangbo, W. J. Jung, J. S. Shu, B. S. Koo, H. B. Krishna, and K. Y. Kim. 2003. PQQ-Dependent organic acid production and effect on common bean growth by Rhizobium tropici CIAT 899. J. Microbiol. Biotechnol. 13(6): 955-959
  6. Choi, C., B. S. Hong, H. Y. Sung, H. S. Lee, and J. H. Kim. 1999. Optimization of extracellular 5-aminolevulinic acid production from Escherichia coli transformed with ALA synthase gene of Bradyrhizobium japonicum. Biotech. Lett. 21: 551-554
  7. Donovan, R. S., C. W. Robinson, and B. R. Glick. 2000. Optimizing the expression of a monoclonal antibody fragment under the transcriptional control of the Escherichia coli lac promoter. Can. J. Microbiol. 46: 532-541
  8. Glick, B. R. 1995. Metabolic load and heterologous gene expression. Biotechnol. Adv. 13: 247-261 https://doi.org/10.1016/0734-9750(95)00004-A
  9. Gong, J., G. A. Hunters, and G. C. Ferreira. 1998. Aspartate 279 in aminolevulinic acid synthase affects enzyme catalysis through enhancing the function of the pyridoxal 5-phosphate cofactor. Biochemistry 37: 3509-3517
  10. Hotta, Y., T. Tanaka, H. Takaoka, Y. Takeuchi, and M. Konnai. 1997. New physiological effects of 5-aminolevulinic acid in plants: The increase of photosynthesis, chlorophyll content, and plant growth. Biosci. Biotechnol. Biochem. 61: 2025-2028
  11. Hunters, G. and G. C. Ferreira. 1999. Pre-steady-state reaction of 5-aminolevulinic acid synthase. J. Biol. Chem. 274: 12222-12228
  12. Ishino, A., A. Magara, M. Tajima, Y. Tuji, K. Takahashi, T. Tanaka, and Y. Hotta. 1999. External medicine for head hair. Jpn Kokai Tokkyo Koho: Toku Kai Hei 11-116446
  13. Jaffe, E. K. and S. Rajagopalan. 1990. Nuclear magnetic resonance studies of 5-aminolevulinate demonstrate multiple forms in aqueous solution. Bioorg. Chem. 18: 381-394
  14. Jordan, P. M. 1991. Biosynthesis of Tetrapyrroles. New Comprehensive Biochemistry. Elsevier, Amsterdam. 19: 1-24
  15. Klotsky, R. A. and I. Schwartz. 1987. Measurement of cat expression from growth-rate-regulated promoters employing $\beta$-lactamase activity as an indicator of plasmid copy number. Gene 55: 141-146
  16. Kosinski, M. J., U. Rinas, and J. E. Bailey. 1992. Isopropylb- d-thiogalactopyranoside influences the metabolism of Escherichia coli. Appl. Microbiol. Biotechnol. 36: 782- 783
  17. Kriegmair, M., R. Baumgartner, R. Kneuchei, H. Stepp, F. Hofstadter, and A. Pofstertter. 1996. Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. J. Urology 165: 105-110
  18. Laemmli, U. K. 1970. Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature 227: 680-685 https://doi.org/10.1038/227680a0
  19. Lascelles, J. 1978. Regulation of pyrrole synthesis, pp. 795- 808. In R. K. Clayton and W. R. Sistrom (eds.), The Photosynthetic Bacteria. Plenum Press, New York. U.S.A
  20. Lee, D. H., W. J. Jun, K. M. Kim, D. H. Shin, H. Y. Cho, and B. S. Hong. 2003. Inhibition of 5-aminolevulinic acid dehydratase in recombinant Escherichia coli using Dglucose. Enzym. Microb. Tech. 32: 27-34
  21. Levy, J. G. 1995. Photodynamic therapy. Trends Biotechnol. 13: 14-18 https://doi.org/10.1016/S0167-7799(00)88895-2
  22. Lowry, O. H., N. J. Roenbrough, A. L. Farr, and R. J. Randal. 1951. Protein measurement with folin phenol reagent. J. Biol. Chem. 193: 265-275
  23. Malik, Z., J. Hanania, and Y. Nitzan. 1990. New trends in photobiology. Bactericidal effects of photoactivated porphyrinsan alternative approach to antimicrobial drugs. J. Photochem. Photobiol. B. Biol. 5: 281-293
  24. Mariet J van der Werf and J. Gregory Zeikus. 1996. 5- Aminolevulinate production by Escherichia coli containing the Rhodobacter sphaeroides hemA gene. Appl. Environ. Microbiol. 62: 3560-3566
  25. Matsumoto, H., Y. Tanida, and K. Ishizuka. 1994. Pesticide Biochem. 48: 214-219
  26. Mauzerall, S. and S. Granick, S. 1956. The occurrence and determination of $\delta$-aminolevulinic acid and porphobilinogen in urine. J. Biol. Chem. 219: 435-442
  27. McClung, C. R., J. E. Somerville, M. L. Guerinot, and B. K. Chelm. 1987. Structure of the Bradyrhizobium japonicum gene hemA encoding 5-aminolevulinic acid synthase. Gene 54: 133-139
  28. Mitchell, L. W. and E. K. Jaffe. 1993. Porphobilinogen synthase from Escherichia coli is a Zn(II) metalloenzyme stimulated by Mg(II). Arch. Biochem. Biophys. 300: 169- 177
  29. Nandi, D. L. and D. Shemin. 1968. Delta-aminolevulinic acid dehydratase of Rhodopseudomonas spheroides. 3. Mechanism of porphobilinogen synthesis. J. Biol. Chem. 243: 1236-1242
  30. Nandi, D. L. and D. Shemin. 1997. Quaternary structure of 5-aminolevulinic acid synthase from Rhodopseudomonas sphaeroides. J. Biol. Chem. 252: 2278-2280
  31. Neidle, E. L. and S. Kaplan. 1993. Expression of the Rhodobacter sphaeroides hemA and hemT genes, encoding two 5-aminolevulinic acid synthase isozymes. J. Bacteriol. 175: 2292-2303
  32. Oh, K. S., D. K. Na, M. H. Kweon, and H. J. Sung. 2003. Expression and purification of delta sleep-inducing peptide in Escherichia coli. J. Microbiol. Biotechnol. 13(4): 620- 623
  33. Peng, Q., H. F. Berg, J. Moan, M. Kongshaug, and J. M. Neslang. 1997. 5-Aminolevulinic acid-based photodynamic therapy: Principle and experimental research. Photochem. Photobiol. 65: 235-251
  34. Rebeiz, C. A., J. A. Juvik, and C. C. Rebeiz. 1988. Porphyric insecticides. 1. Concept and phenomenology. Pestic. Biochem. Physiol. 30: 11-27 https://doi.org/10.1016/0048-3575(88)90055-7
  35. Rebeiz, C. A., A. Montazer-Zouhoor, J. M. Mayasich, B. C. Tripathy, S. M. Wu, and C. C. Rebeiz. 1988. Photodynamic herbicides. Recent developments and molecular basis of selectivity. Crit. Rev. Plant Sci. 6: 385-436
  36. Sasaki, K., T. Tananka, Y. Nishizawa, and M. Hayashi. 1991. Enhanced production of 5-aminolevulinic acid by repeated addition of levulinic acid and supplement of precursors in photoheterotrophic culture of Rhodobacter sphaeroides. J. Ferment. Bioeng. 71: 403-406
  37. Sasaki, K., T. Tanaka, N. Nishio, and S. Nagai. 1993. Effect of culture pH on the extracellular production of $\delta$-aminolevulinic acid by Rhodobacter sphaeroides from volatile fatty acids. Biotech. Lett. 15: 859-864
  38. Sasikala, C., C. V. Ramana, and R. P. Raghuveer. 1994. 5- Aminolevulinic acid: A potential herbicide/insecticide from microorganisms. Biotechnol. Prog. 10: 451-459
  39. Takeya, H., T. Tanaka, T. Hotta, and K. Sasaki. 1997. Production methods and applications of 5-aminolevulinic acid. Porphyrins 6: 127-135
  40. Vladimir, Y. B., A. L. Demain, and N. I. Zaitseva. 1997. The crucial contribution of starved resting cells to the elucidation of the pathway of vitamin B12 biosynthesis. Crit. Rev. Biotechnol. 17: 21-37
  41. Watanabe, K., T. Tanaka, Y. Hotta, H. Kuramochi, and Y. Takeuchi. 2000. Improving salt tolerance of cotton seedlings with 5-aminolevulinic acid. Plant Growth Regul. 32: 97- 101