Skip to main content
SpringerLink
Log in

Fermentative production of shikimic acid: a paradigm shift of production concept from plant route to microbial route

  • Original Paper
  • Published:
Bioprocess and Biosystems Engineering Aims and scope Submit manuscript

Abstract

Different physiological and nutritional parameters affect the fermentative production of shikimic acid. In our study, Citrobacter freundii initially produced 0.62 g/L of shikimic acid in 72 h. However, when process optimization was employed, 5.11 g/L of shikimic acid was produced in the production medium consisting of glucose (5.0 %), asparagine (4.5 %), CaCO3 (2.0 %), at pH 6.0, when inoculated with 6 % inoculum and incubated at 30 ± 1 °C, 200 rpm for 60 h. Preliminary fed-batch studies have resulted in the production of 9.11 g/L of shikimic acid on feeding the production medium by 20 g/L of glucose at 24 h of the fermentation run. Production of similar amount of shikimic acid was observed when the optimized conditions were employed in a 10-L bioreactor as obtained in shake flask conditions. A total of 9.11 g/L of shikimic acid was produced in 60 h. This is approximately 14.69-fold increase in shikimic acid production when compared to the initial un-optimized production conditions. This has also resulted in the reduction of the production time. The present study provides useful information to the industrialists seeking environmentally benign technology for the production of bulk biomolecules through manipulation of various chemical parameters.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Stavric B, Stolz DR (1976) Shikimic acid. Fd Cosmet Toxicol 14(2):141–145

    Article  CAS  Google Scholar 

  2. Evans IA, Osman MA (1974) Carcinogenicity of bracken and shikimic acid. Nature 250:348–349

    Article  CAS  Google Scholar 

  3. Gibson MI, Gibson F, Doy CH, Morgan PN (1962) Nature 195:1173

    Article  CAS  Google Scholar 

  4. Bradley D (2005) Star role for bacteria in controlling flu pandemic. Nat Rev Drug Discov 4(12):945–946

    Article  CAS  Google Scholar 

  5. Kim CU, Lew W, Williams MA, Liu H, Zhang L, Swaminathan S, Bischhofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (1997) Influenza neuraminidase inhibitors possessing novel hydrophobic interaction in the enzyme active site: design, synthesis and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 119:681–690

    Article  CAS  Google Scholar 

  6. Rohloff JC, Kent KM, Postich MJ, Becker MW, Chapman HH, Kelly DE, Lew W, Louie MS, McGee LR, Prisbe EJ, Schultze LM, Yu RH, Zhang L (1998) Practical total synthesis of the anti-influenza drug GS-4104. J Org Chem 63(13):4545–4550

    Article  CAS  Google Scholar 

  7. Bongaerts J, Kramer M, Muller U, Raeven L, Wubbolts M (2001) Metabolic engineering for microbial production of aromatic amino acids and derived compounds. Metab Eng 3:289–300

    Article  CAS  Google Scholar 

  8. Kramer M, Bongaerts J, Bovenberg R, Kremer S, Muller U, Orf S, Wubbolts M, Raeven L (2003) Metabolic engineering for microbial production of shikimic acid. Metab Eng 5:277–283

    Article  CAS  Google Scholar 

  9. Shirai M, Miyata R, Sasaki S, Sakamoto K, Yahanda S, Shibayama K, Yonehara T, Ogawa K (2001) Micro-organism belonging to the genus Citrobacter and process for producing shikimic acid. European patent. EP 1 092 766 A1

  10. Escalante A, Calderon R, Valdiviya A, de Anda R, Hernandez G, Ramirez OT, Gosset G, Bolivar F (2010) Metabolic engineering for the production of shikimic acid in an evolved Escherichia coli strain lacking the phosphoenolpyruvate: carbohydrate phosphotransferase system. Microb Cell Factories 9:21

    Article  Google Scholar 

  11. Chandran SS, Yi J, Draths KM, von Dainiken R, Meber W, Frost JW (2003) Phosphoenolpyruvate availability and the biosynthesis of shikimic acid. Biotechnol Prog 19:808–814

    Article  CAS  Google Scholar 

  12. Bogosian G, Frantz JP, Glendale MO (2011) Use of glyphosate to produce shikimic acid in microorganisms. US patent. US 2011/0020885 A1

  13. Johansson L, Liden G (2006) Transcriptone analysis of a shikimic acid producing strain of Escherichia coli W3110 grown under carbon- and phosphate-limited conditions. J Biotechnol 126:528–545

    Article  CAS  Google Scholar 

  14. Johansson A, Lindskog G, Silversparre CC, Nielson KF, Liden G (2005) Shikimic acid production by a modified strain of Escherichia coli (W3110.shik1) under phosphate limited and carbon limited conditions. Biotechnol Bioeng 92:541–552

    Article  CAS  Google Scholar 

  15. Knop DR, Draths KM, Chandran SS, Barker JL, Frost JW (2001) Hydroaromatic equilibrium during biosynthesis of shikimic acid. J Am Chem Soc 123:10173–10182

    Article  CAS  Google Scholar 

  16. Li K, Mikola MR, Draths KM, Worden RM, Frost JW (1999) Fed-batch fermenter synthesis of 3-dehydroshikimic acid using recombinant Escherichia coli. Biotechnol Bioeng 64(1):61–73

    Article  CAS  Google Scholar 

  17. Rangachari S, Friedman TC, Hartmann G, Hemminghaus JW, Kretzmer KA, Nissing NJ, Weisenfeld RB (2009) Process for recovering shikimic acid. European patent. EP 2 201 123 B1

  18. Iomantas Y, Abalakina EG, Polanuer B, Yampolskaya TA, Kozlov JI (2002) Method of producing shikimic acid. US patent. US 6,436,664 B1

  19. Ahn JO, Lee HW, Saha R, Park MS, Jung JK, Lee DY (2008) Exploring the effects of carbon sources on the metabolic capacity for shikimic acid production in Escherichia coli using Insilico metabolic prediction. J Microbiol Biotechnol 18(11):1773–1784

    CAS  Google Scholar 

  20. Simonart P, Wiaux A (1960) Production of shikimic acid by Penicillium griseofulvum Dierckx. Nature 186:78–79

    Article  CAS  Google Scholar 

  21. Shida T, Komagatai K, Mitsugi K (1975) Effect of inoculum in bacterial growth size and nutrients. J Gen Appl Microbiol 21:75–86

    Article  Google Scholar 

  22. Casida LE (1997) Industrial microbiology. New Age International (P) Ltd Publishers, New Delhi

    Google Scholar 

Download references

Acknowledgments

Authors wish to acknowledge the financial support from Indian Council of Medical Research (ICMR) to carry out this work.

Author information

Authors and Affiliations

  1. Department of Microbiology, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India

    Priyanka Tripathi, Garima Rawat, Sweta Yadav & R. K. Saxena

Authors
  1. Priyanka Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Garima Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sweta Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. K. Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. K. Saxena.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tripathi, P., Rawat, G., Yadav, S. et al. Fermentative production of shikimic acid: a paradigm shift of production concept from plant route to microbial route. Bioprocess Biosyst Eng 36, 1665–1673 (2013). https://doi.org/10.1007/s00449-013-0940-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00449-013-0940-4

Keywords

Search

Navigation