Issue
Korean Journal of Chemical Engineering,
Vol.32, No.4, 702-706, 2015
Establishment of a biosynthesis pathway for (R)-3-hydroxyalkanoates in recombinant Escherichia coli
A biosynthetic pathway for the production of (R)-3-hydroxyalkanoates (R3HAs) through in vivo depolymerization of poly(3-hydroxyalkanoates) [P(3HAs)] was constructed in recombinant Escherichia coli fadA mutant WA101 by introducing the Pseudomonas sp. 61-3 PHA synthase gene (phaC2) and the P. aeruginosa intracellular PHA depolymerase gene (phaZ). When recombinant E. coli WA101 strain expressing the phaC2 gene and the phaZ gene was cultured in Luria-Bertani (LB) medium containing 2 g/L of sodium decanoate, R3HAs could be produced to the concentration of 0.49 g/L. The mole fraction of R3HAs was 7.5mol% of 3-hydroxybutyrate (3HB), 31.6mol% of 3-hydroxyhexanoate (3HHx), 30 mol% of 3-hydroxyoctanoate (3HO), 29.4mol% of 3-hydroxydecanoate (3HD), and 1.5mol% of 3-hydroxydodecanoate (3HDD). When the E. coli 3-ketoacyl-ACP reductase gene (fabG) was overexpressed to provide more (R)-3-hydroxyacyl-CoA (R3HA-CoA), the concentration of R3HAs was increased up to 1.05 g/L. Also, expression of the fabG gene resulted in the mole fraction change of produced R3HAs, in which 3HD fraction was enriched from 29.4mol% to 57.9mol% with the decrease of 3HHx fraction from 31.6mol% to 9.6mol%. Interestingly, the only expression of the fabG gene in E. coli WA101 could produce R3HAs to 0.55 g/L, which suggests that E. coli might have unidentified CoA hydrolases that have substrate specificities toward R3HA-CoA. This study shows the enantiomerically pure RHAs can be efficiently produced by metabolically engineered E. coli with high yield.
[References]
  1. Chiba T, Nakai T, Chem. Lett., 161, 651, 1985
  2. Madison LL, Huisman GW, Microbiol. Mol. Biol. Rev., 63, 21, 1999
  3. Lee SY, Biotechnol. Bioeng., 49(1), 1, 1996
  4. Steinbuchel A, Valentin HE, Fems Microbiol. Lett, 128, 219, 1995
  5. Lee Y, Park SH, Lim IT, Han KB, Lee SY, Enzyme Microb. Technol., 27(1-2), 33, 2000
  6. de Roo G, Kellerhals MB, Ren Q, Witholt B, Kessler B, Biotechnol. Bioeng., 77(6), 717, 2002
  7. Zhao K, Tian G, Zheng Z, Chen JC, Chen GQ, Fems Microbiol. Lett, 218, 59, 2003
  8. Gao HJ, Wu Q, Chen GQ, Fems Microbiol. Lett, 213, 59, 2002
  9. Zheng Z, Zhang MJ, Zhang G, Chen GQ, Antonie Van Leeuwenhoek, 85, 93, 2004
  10. Lee SY, Lee Y, Wang FL, Biotechnol. Bioeng., 65(3), 363, 1999
  11. Lee SY, Lee Y, Appl. Environ. Microbiol., 69, 3421, 2003
  12. Park SJ, Park JP, Lee SY, Fems Microbiol. Lett, 214, 217, 2002
  13. Park SJ, Park JP, Lee SY, Doi Y, Enzyme Microb. Technol., 33(1), 62, 2003
  14. Sambrook J, Russel DW, Molecular cloning: A laboratory manual. 3rd Ed. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, NY (2001)., 2001
  15. Timm A, Steinbuchel A, Eur. J. Biochem., 209, 15, 1992
  16. Braunegg G, Sonnleitner B, Lafferty RM, Eur. J. Appl. Microbiol. Biotechnol., 6, 29, 1978
  17. Choi J, Lee SY, Shin K, Lee WG, Park SJ, Chang HN, Chang YK, Biotechnol. Bioprocess Eng., 7, 371, 2002
  18. Matsusaki H, Manji S, Taguchi K, Kato M, Fukui T, Doi Y, J. Bacteriol., 180, 6459, 1998
  19. Fiedler S, Steinbuchel A, Rehm BHA, Arch. Microbiol., 178, 149, 2002
  20. Park SJ, Lee SY, J. Bacteriol., 185, 5391, 2003
  21. Ren Q, Sierro N, Witholt B, Kessler B, J. Bacteriol., 182, 2978, 2000
  22. Taguchi K, Aoyagi Y, Matsusaki H, Fukui T, Doi Y, Fems Microbiol. Lett, 176, 183, 1999
  23. Tsuge T, Fukui T, Matsusaki H, Taguchi S, Kobayashi G, Ishizaki A, Doi Y, Fems Microbiol. Lett, 184, 193, 2000
  24. Tsuge T, Taguchi K, Taguchi S, Doi Y, Int. J. Biol. Macromol., 31, 195, 2003
  25. Rehm BHA, Kruger N, Steinbuchel A, J. Biol. Chem., 273, 24044, 1998
  26. Park SJ, Lee SY, Lee Y, Appl. Biochem. Biotechnol., 114, 373, 2004
  27. de Roo G, Kellerhals MB, Ren Q, Witholt B, Kessler B, Biotechnol. Bioeng., 77(6), 717, 2002
  28. Liu Q, Luo G, Zhou XR, Chen GQ, Metab. Eng., 13, 11, 2011