Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Exploring the Effects of Carbon Sources on the Metabolic Capacity for Shikimic Acid Production in Escherichia coli Using In Silico Metabolic Predictions

  • Ahn, Jung-Oh (Division of Biotechnology R&BD, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hong-Weon (Division of Biotechnology R&BD, Korea Research Institute of Bioscience and Biotechnology) ;
  • Saha, Rajib (Department of Chemical and Biomolecular Engineering, National University of Singapore) ;
  • Park, Myong-Soo (Division of Biotechnology R&BD, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jung, Joon-Ki (Division of Biotechnology R&BD, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Dong-Yup (Department of Chemical and Biomolecular Engineering, National University of Singapore)
  • Published : 2008.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Effects of various industrially important carbon sources (glucose, sucrose, xylose, gluconate, and glycerol) on shikimic acid (SA) biosynthesis in Escherichia coli were investigated to gain new insight into the metabolic capability for overproducing SA. At the outset, constraints-based flux analysis using the genome-scale in silico model of E. coli was conducted to quantify the theoretical maximum SA yield. The corresponding flux distributions fueled by different carbon sources under investigation were compared with respect to theoretical yield and energy utilization, thereby identifying the indispensable pathways for achieving optimal SA production on each carbon source. Subsequently, a shikimate-kinase-deficient E. coli mutant was developed by blocking the aromatic amino acid pathway, and the production of SA on various carbon sources was experimentally examined during 51 batch culture. As a result, the highest production rate, 1.92 mmol SA/h, was obtained when glucose was utilized as a carbon source, whereas the efficient SA production from glycerol was obtained with the highest yield, 0.21 mol SA formed per mol carbon atom of carbon source consumed. The current strain can be further improved to satisfy the theoretically achievable SA production that was predicted by in silico analysis.

Keywords

References

  1. Bare-Viveros, J. L., J. Osuna, G. Hernandez-Chavez, X. Soberon, F. Bolivar, and G. Gosset. 2004. Metabolic engineering and protein directed evolution increase the yield of L-phenylalanine synthesized from glucose in Escherichia coli. Biotechnol. Bioeng. 87: 516-524 https://doi.org/10.1002/bit.20159
  2. Bockmann, J., H. Heuwl, and J. W. Lengeler. 1992. Characterization of a chromosomally encoded, non-PTS metabolic pathway for sucrose utilization in Escherichia coli EC3132. Mol. Gen. Genet. 235: 22-32 https://doi.org/10.1007/BF00286177
  3. Bradley, D. 2005. Star role for bacteria in controlling flu pandemic? Nat. Rev. Drug Discov. 4: 945-946 https://doi.org/10.1038/nrd1917
  4. Chandran, S. S., J. Yi, and K. M. Draths. 2003. Phosphoenolpyruvate availability and the biosynthesis of shikimic acid. Biotechnol. Prog. 19: 808-814 https://doi.org/10.1021/bp025769p
  5. Datsenko, K. A. and B. L. Wanner. 2000. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl. Acad. Sci. USA 97: 6640-6645
  6. De Clercq, E. 2002. Strategies in the design of antiviral drugs. Nat. Rev. Drug Discov. 1: 13-25 https://doi.org/10.1038/nrd703
  7. Draths, K. M., D. L. Phmpliano, D. L. Conley, J. W. Frost, A. Berry, G. L. Disbrow, R. J. Staversk, and J. C. Lievense. 1992. Biocatalytic synthesis of aromatics from D-glucose: The role of transketolase. J. Am. Chem. Soc. 114: 3956-3962 https://doi.org/10.1021/ja00036a050
  8. Draths, K., D. R. Knop, and J. W. Frost. 1999. Shikimic acid and quininc acid: Replacing isolation from plant sources with recombinant microbial biocatalysis. J. Am. Chem. Soc. 121: 1603-1604 https://doi.org/10.1021/ja9830243
  9. Driessen, M., P. W. Postma, and K. van Dam. 1987. Energetics of glucose uptake in Salmonella typhimurium. Arch. Microbiol. 146: 358-361 https://doi.org/10.1007/BF00410936
  10. Feist, A. M., C. S. Henry, J. L. Reed, M. Krummenacker, A. R. Joyce, P. D. Karp, L. J. Broadbetl, V. Hatzimanikatis, and B. O. Palsson. 2007. A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol. Syst. Biol. 3: 1-18
  11. Flores, N., J. Xiao, A. Berry, F. Bolivar, and F. Valle. 1996. Pathway engineering for the production of aromatic compounds in Escherichia coli. Nat. Biotechnol. 14: 620-623 https://doi.org/10.1038/nbt0596-620
  12. Gosset, G., J. Yong-Xiao, and A. Beery. 1996. A direct comparison of approaches for increasing carbon flow to aromatic biosynthesis in Escherichia coli. J. Ind. Microbiol. 17: 47-52 https://doi.org/10.1007/BF01570148
  13. Hendereson, P. J. and E. O. Davis. 1987. The cloning and DNA sequence of the gene xylE for xylose-proton symport in Escherichia coli K12. J. Biol. Chem. 262: 13928-13932
  14. Hong, S. H., S. Y. Moon, and S. Y. Lee. 2003. Prediction of maximum yields of metabolites and optimal pathways for their production by metabolic flux analysis. J. Microbiol. Biotechnol. 13: 571-577
  15. Honisch, C., A. Raghunathan, C. R. Cantor, B. O. Palsson, and D. van den Boom. 2004. High-throughput mutation detection underlying adaptive evolution of Escherichia coli-K12. Genome Res. 14: 2495-2502 https://doi.org/10.1101/gr.2977704
  16. Johansson, L., A. Lindskog, G. Silfversparre, C. Cimander, K. F. Nielsen, and G. Liden. 2005. Shikimic acid production by a modified strain of E. coli (W3110.shik1) under phosphatelimited and carbon-limited conditions. Biotechnol. Bioeng. 92: 541-552 https://doi.org/10.1002/bit.20546
  17. Kim, C. U., W. Lew, M. A. Williams, L. Zhang, H. Liu, S. Swaminathan, et al. 1997. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: Design, synthesis, and structural analysis of carbocyclic sialic acid analogs with potent anti-influenza activity. J. Am. Chem. Soc. 119: 681-690 https://doi.org/10.1021/ja963036t
  18. Kim, P. J., D.-Y. Lee, T. Y. Kim, K. H. Lee, H. Jeong, S. Y. Lee, and S. Park. 2007. Metabolite-essentiality elucidates robustness of Escherichia coli metabolism. Proc. Natl. Acad. Sci. USA 104: 13638-13642
  19. Knop, D. R., K. M. Draths, S. S. Chandra, J. L. Barker, R. V. Daeniken, W. Weber, and J. W. Frost. 2001. Hydroaromatic equilibration during biosynthesis of shikimic acid. J. Am. Chem. Soc. 123: 10173-10182 https://doi.org/10.1021/ja0109444
  20. Lee, D.-Y., H. Yun, S. Park, and S. Y. Lee. 2003. MetaFluxNet: The management of metabolic reaction information and quantitative metabolic flux analysis. Bioinformatics 19: 2144-2146 https://doi.org/10.1093/bioinformatics/btg271
  21. Lu, J. and J. C. Liao. 1997. Metabolic engineering and control analysis for production of aromatics: Role of transaldolase. Biotechnol. Bioeng. 53: 132-138 https://doi.org/10.1002/(SICI)1097-0290(19970120)53:2<132::AID-BIT2>3.0.CO;2-P
  22. Miller, J. E., K. C. Backman, J. M. O'Connor, and T. R. Hatch. 1987. Production of phenylalanine and organic acids by phosphoenolpyruvate carboxylase-deficient mutants of Escherichia coli. J. Ind. Microbiol. 2: 143-149 https://doi.org/10.1007/BF01569421
  23. Patnaik, R. and J. C. Liao. 1994. Engineering of Escherichia coli central metabolism for aromatic metabolite production with near theoretical yield. Appl. Environ. Microbiol. 6: 3903-3908
  24. Patnaik, R., W. D. Roof, R. F. Young, and J. C. Liao. 1992. Stimulation of glucose catabolism in Escherichia coli by a potential futile cycle. J. Bacteriol. 174: 7527-7532 https://doi.org/10.1128/jb.174.23.7527-7532.1992
  25. Pharkya, P., A. P. Burgard, and C. D. Maranas. 2003. Exploring the overexpression of amino acids using the bilevel optimization framework OptKnock. Biotechnol. Bioeng. 84: 887-899 https://doi.org/10.1002/bit.10857
  26. Reed, J. L. and B. O. Palsson. 2004. Genome-scale in silico models of E. coli have multiple equivalent phenotypic states: Assessment of correlated reaction subsets that comprise network states. Genome Res. 14: 1797-1805 https://doi.org/10.1101/gr.2546004
  27. Reed, J. L., T. D. Vo, C. H. Schilling, and B. O. Palsson. 2003. An expanded genome-scale model of Escherichia coli K- 12(iJR904 GSM/GPR). Genome Biol. 4: R54.1-R54.12 https://doi.org/10.1186/gb-2003-4-9-r54
  28. Schmid, K., M. Schupfner, and R. Schmitt. 1982. Plasmidmediated uptake and sucrose metabolism in Escherichia coli K12: Mapping of the scr genes of pUR400. Mol. Microbiol. 2: 1-8 https://doi.org/10.1111/j.1365-2958.1988.tb00001.x
  29. Schuetz, R., L. Kuepfer, and U. Sauer. 2007. Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli. Mol. Syst. Biol. 3: 1-15
  30. Stephanopoulos, G. and J. J. Vallino. 1991. Network rigidity and metabolic engineering in metabolite overproduction. Science 252: 1675-1681 https://doi.org/10.1126/science.1904627
  31. Sumiya, M., E. O. Davis, L. C. Packman, T. P. McDonald, and P. J. Henderson. 1995. Molecular genetics of a receptor protein for D-xylose, encoded by the gene xylF in Escherichia coli. Receptors Channels 3: 117-128
  32. Varma, A. and B. O. Palsson. 1994. Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. Appl. Environ. Microbiol. 60: 3724-3731
  33. Weaver, L. M. and K. M. Herrmann. 1990. Cloning of an aroF allele encoding a tyrosine-insensitive 3-deoxy-D-arabionheptulosonate 7-phosphate synthase. J. Bacteriol. 172: 6581-6584 https://doi.org/10.1128/jb.172.11.6581-6584.1990
  34. Yi, J., K. Li, K. M. Draths, and J. W. Frost. 2002. Modulation of phosphoenolpyruvate synthase expression increases shikimate pathway product yields in E. coli. Biotechnol. Prog. 18: 1141-1148 https://doi.org/10.1021/bp020101w
  35. Yi, J., K. M. Draths, and J. W. Frost. 2003. Altered glucose transport and shikimate pathway product yields in E. coli. Biotechnol. Prog. 19: 1450-1459 https://doi.org/10.1021/bp0340584

Cited by

  1. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid vol.3, pp.7, 2008, https://doi.org/10.1002/cssc.201000111
  2. A bacterial platform for fermentative production of plant alkaloids vol.2, pp.1, 2008, https://doi.org/10.1038/ncomms1327
  3. Constitutive expression of selected genes from the pentose phosphate and aromatic pathways increases the shikimic acid yield in high-glucose batch cultures of an Escherichia coli strain lacking PTS vol.12, pp.None, 2008, https://doi.org/10.1186/1475-2859-12-86
  4. Expanding horizons of shikimic acid : Recent progresses in production and its endless frontiers in application and market trends vol.97, pp.10, 2013, https://doi.org/10.1007/s00253-013-4840-y
  5. Fermentative production of shikimic acid: a paradigm shift of production concept from plant route to microbial route vol.36, pp.11, 2008, https://doi.org/10.1007/s00449-013-0940-4
  6. Engineering Escherichia coli to overproduce aromatic amino acids and derived compounds vol.13, pp.None, 2014, https://doi.org/10.1186/s12934-014-0126-z
  7. (R,S)-Tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli vol.4, pp.None, 2008, https://doi.org/10.1038/srep06695
  8. Metabolic engineering of Escherichia coli to enhance shikimic acid production from sorbitol vol.30, pp.9, 2008, https://doi.org/10.1007/s11274-014-1679-z
  9. Recombinant expression of glpK and glpD genes improves the accumulation of shikimic acid in E. coli grown on glycerol vol.30, pp.12, 2014, https://doi.org/10.1007/s11274-014-1753-6
  10. Microbial transformation of quinic acid to shikimic acid by Bacillus megaterium vol.1, pp.None, 2008, https://doi.org/10.1186/s40643-014-0007-7
  11. Shikimic acid, a base compound for the formulation of swine/avian flu drug: statistical optimization, fed-batch and scale up studies along with its application as an antibacterial agent vol.107, pp.2, 2008, https://doi.org/10.1007/s10482-014-0340-z
  12. Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources vol.5, pp.None, 2008, https://doi.org/10.1038/srep13670
  13. Rational engineering of multiple module pathways for the production of L-phenylalanine in Corynebacterium glutamicum vol.42, pp.5, 2008, https://doi.org/10.1007/s10295-015-1593-x
  14. Improvement of shikimic acid production in Escherichia coli with growth phase-dependent regulation in the biosynthetic pathway from glycerol vol.33, pp.2, 2008, https://doi.org/10.1007/s11274-016-2192-3
  15. Heterologous biosynthesis of natural product naringenin by co-culture engineering vol.2, pp.3, 2017, https://doi.org/10.1016/j.synbio.2017.08.003
  16. Production and Synthetic Modifications of Shikimic Acid vol.118, pp.20, 2008, https://doi.org/10.1021/acs.chemrev.8b00350
  17. Metabolic modeling and response surface analysis of an Escherichia coli strain engineered for shikimic acid production vol.12, pp.1, 2008, https://doi.org/10.1186/s12918-018-0632-4
  18. Production of p -amino- L -phenylalanine ( L -PAPA) from glycerol by metabolic grafting of Escherichia coli vol.17, pp.None, 2008, https://doi.org/10.1186/s12934-018-0996-6
  19. Bioprocess Optimization for the Production of Aromatic Compounds With Metabolically Engineered Hosts: Recent Developments and Future Challenges vol.8, pp.None, 2008, https://doi.org/10.3389/fbioe.2020.00096
  20. Metabolic engineering of Escherichia coli for production of chemicals derived from the shikimate pathway vol.47, pp.6, 2008, https://doi.org/10.1007/s10295-020-02288-2
  21. Biocatalytic routes to anti-viral agents and their synthetic intermediates vol.50, pp.3, 2008, https://doi.org/10.1039/d0cs00763c