Display options
Cite
Martínez JA, Bolívar F, Escalante A. Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production. Front Bioeng Biotechnol. 2015;3:145doi: 10.3389/fbioe.2015.00145.
Martínez, J. A., Bolívar, F., & Escalante, A. (2015). Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production. Frontiers in bioengineering and biotechnology, 3145. https://doi.org/10.3389/fbioe.2015.00145
Martínez, Juan Andrés, et al. "Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production." Frontiers in bioengineering and biotechnology vol. 3 (2015): 145. doi: https://doi.org/10.3389/fbioe.2015.00145
Martínez JA, Bolívar F, Escalante A. Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production. Front Bioeng Biotechnol. 2015 Sep 23;3:145. doi: 10.3389/fbioe.2015.00145. eCollection 2015. PMID: 26442259; PMCID: PMC4585142.
Copy Download .nbib Format: NLM
Share it on

Front Bioeng Biotechnol. 2015 Sep 23;3:145. doi: 10.3389/fbioe.2015.00145. eCollection 2015.

Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production.

Frontiers in bioengineering and biotechnology

Juan Andrés Martínez, Francisco Bolívar, Adelfo Escalante

Affiliations

  1. Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México , Cuernavaca , Mexico.

PMID: 26442259 PMCID: PMC4585142 DOI: 10.3389/fbioe.2015.00145

Abstract

Shikimic acid (SA) is an intermediate of the SA pathway that is present in bacteria and plants. SA has gained great interest because it is a precursor in the synthesis of the drug oseltamivir phosphate (OSF), an efficient inhibitor of the neuraminidase enzyme of diverse seasonal influenza viruses, the avian influenza virus H5N1, and the human influenza virus H1N1. For the purposes of OSF production, SA is extracted from the pods of Chinese star anise plants (Illicium spp.), yielding up to 17% of SA (dry basis content). The high demand for OSF necessary to manage a major influenza outbreak is not adequately met by industrial production using SA from plants sources. As the SA pathway is present in the model bacteria Escherichia coli, several "intuitive" metabolically engineered strains have been applied for its successful overproduction by biotechnological processes, resulting in strains producing up to 71 g/L of SA, with high conversion yields of up to 0.42 (mol SA/mol Glc), in both batch and fed-batch cultures using complex fermentation broths, including glucose as a carbon source and yeast extract. Global transcriptomic analyses have been performed in SA-producing strains, resulting in the identification of possible key target genes for the design of a rational strain improvement strategy. Because possible target genes are involved in the transport, catabolism, and interconversion of different carbon sources and metabolic intermediates outside the central carbon metabolism and SA pathways, as genes involved in diverse cellular stress responses, the development of rational cellular strain improvement strategies based on omics data constitutes a challenging task to improve SA production in currently overproducing engineered strains. In this review, we discuss the main metabolic engineering strategies that have been applied for the development of efficient SA-producing strains, as the perspective of omics analysis has focused on further strain improvement for the production of this valuable aromatic intermediate.

Keywords: Escherichia coli; antiviral drug; influenza; metabolic engineering; metabolome; shikimic acid; transcriptome

References

  1. Appl Environ Microbiol. 1994 Nov;60(11):3903-8 - PubMed
  2. Curr Opin Biotechnol. 2012 Aug;23(4):617-23 - PubMed
  3. Appl Microbiol Biotechnol. 2012 Jun;94(6):1483-94 - PubMed
  4. J Bacteriol. 2007 Jan;189(2):603-10 - PubMed
  5. J Mol Microbiol Biotechnol. 2007;13(1-3):105-16 - PubMed
  6. Curr Opin Biotechnol. 2014 Oct;29:39-45 - PubMed
  7. Curr Opin Biotechnol. 2004 Feb;15(1):64-9 - PubMed
  8. Chem Pharm Bull (Tokyo). 2006 Oct;54(10):1459-61 - PubMed
  9. Biotechnol Bioeng. 2003 Dec 30;84(7):887-99 - PubMed
  10. Mini Rev Med Chem. 2012 Dec;12(14):1443-54 - PubMed
  11. Trends Biotechnol. 2003 Apr;21(4):162-9 - PubMed
  12. BMC Genomics. 2010 Nov 11;11:628 - PubMed
  13. Comput Struct Biotechnol J. 2012 Nov 12;3:e201210009 - PubMed
  14. Curr Opin Biotechnol. 2015 Dec;35:23-9 - PubMed
  15. Biotechnol Prog. 2002 Nov-Dec;18(6):1141-8 - PubMed
  16. BMC Genomics. 2012 Aug 10;13:385 - PubMed
  17. Biotechnol Bioeng. 1995 May 20;46(4):361-70 - PubMed
  18. PLoS Comput Biol. 2014 Apr 24;10(4):e1003580 - PubMed
  19. Curr Opin Biotechnol. 2009 Dec;20(6):651-8 - PubMed
  20. Nucleic Acids Res. 2013 Jan;41(Database issue):D605-12 - PubMed
  21. Bioresour Technol. 2012 Sep;119:141-7 - PubMed
  22. Int J Biol Macromol. 2014 Jul;68:173-7 - PubMed
  23. PLoS One. 2009 Sep 04;4(9):e6903 - PubMed
  24. Bioresour Technol. 2012 Jun;114:549-54 - PubMed
  25. Metab Eng. 2001 Oct;3(4):289-300 - PubMed
  26. Curr Opin Biotechnol. 2014 Oct;29:156-62 - PubMed
  27. Biotechnol Bioeng. 2001 Jun 20;73(6):530-5 - PubMed
  28. Microb Cell Fact. 2010 Apr 12;9:21 - PubMed
  29. Trends Biochem Sci. 2001 Mar;26(3):179-86 - PubMed
  30. J Ethnopharmacol. 2011 Jun 14;136(1):10-20 - PubMed
  31. Biotechnol Adv. 2012 Nov-Dec;30(6):1425-31 - PubMed
  32. Biotechnol Adv. 2013 Dec;31(8):1200-23 - PubMed
  33. Metab Eng. 2003 Oct;5(4):277-83 - PubMed
  34. Metab Eng. 2008 Mar;10(2):69-77 - PubMed
  35. J Am Chem Soc. 2001 Oct 24;123(42):10173-82 - PubMed
  36. J Biotechnol. 2006 Dec 1;126(4):528-45 - PubMed
  37. Curr Opin Biotechnol. 2015 Aug;34:125-34 - PubMed
  38. Curr Opin Biotechnol. 2015 Aug;34:135-41 - PubMed
  39. Bioresour Technol. 2014 Aug;166:64-71 - PubMed
  40. Metab Eng. 2014 Sep;25:50-62 - PubMed
  41. Curr Opin Microbiol. 2011 Oct;14(5):599-607 - PubMed
  42. Metab Eng. 2004 Oct;6(4):285-93 - PubMed
  43. Mol Syst Biol. 2007;3:119 - PubMed
  44. Nat Biotechnol. 1996 May;14(5):620-3 - PubMed
  45. Comput Struct Biotechnol J. 2014 Aug 27;11(18):28-34 - PubMed
  46. Microb Cell Fact. 2013 Sep 30;12:86 - PubMed
  47. Biotechnol Prog. 2003 May-Jun;19(3):808-14 - PubMed
  48. Appl Environ Microbiol. 2012 Jan;78(1):89-98 - PubMed
  49. Microb Cell Fact. 2015 May 17;14:71 - PubMed
  50. Microb Cell Fact. 2014 Feb 10;13:21 - PubMed
  51. Microb Cell Fact. 2014 Feb 21;13(1):28 - PubMed
  52. Biotechnol Bioeng. 2004 Aug 20;87(4):516-24 - PubMed
  53. Comput Struct Biotechnol J. 2013 Jan 16;3:e201210018 - PubMed
  54. Microb Cell Fact. 2014 Sep 09;13(1):126 - PubMed
  55. Biotechnol Bioeng. 2005 Dec 5;92(5):541-52 - PubMed
  56. Curr Opin Microbiol. 2004 Oct;7(5):513-8 - PubMed

Publication Types