Display options
Share it on

Metabolomics. 2018 Jul 04;14(7):96. doi: 10.1007/s11306-018-1386-0.

Identifying metabolic elements that contribute to productivity of 1-propanol bioproduction using metabolomic analysis.

Metabolomics : Official journal of the Metabolomic Society

Sastia Prama Putri, Yasumune Nakayama, Claire Shen, Shingo Noguchi, Katsuaki Nitta, Takeshi Bamba, Sammy Pontrelli, James Liao, Eiichiro Fukusaki

Affiliations

  1. Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. [email protected].
  2. Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  3. Department of Applied Microbial Technology, Sojo University, 4-22-1 Ikeda, Kumamoto, 860-0082, Japan.
  4. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 300, Taiwan, Republic of China.
  5. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA, 90095, USA.
  6. Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Shinagawa R&D Center, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
  7. Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8285, Japan.

PMID: 30830363 DOI: 10.1007/s11306-018-1386-0

Abstract

INTRODUCTION: Previously constructed Escherichia coli strains that produce 1-propanol use the native threonine pathway, or a heterologous citramalate pathway. However, based on the energy and cofactor requirements of each pathway, a combination of the two pathways produces synergistic effects that increase the theoretical maximum yield with a simultaneous unexplained increase in productivity.

OBJECTIVE: Identification of key factors that contribute to synergistic effect leading to 1-propanol yield and productivity improvement in E. coli with native threonine pathway and heterologous citramalate pathway.

METHOD: A combination of snapshot metabolomic profiling and dynamic metabolic turnover analysis were used to identify system-wide perturbations that contribute to the productivity improvement.

RESULT AND CONCLUSION: In the presence of both pathways, increased glucose consumption and elevated levels of glycolytic intermediates are attributed to an elevated phosphoenolpyruvate (PEP)/pyruvate ratio that is known to increase the function of the native phosphotransferase. Turnover analysis of nitrogen containing byproducts reveals that ammonia assimilation, required for the threonine pathway, is streamlined when provided with an NAD(P)H surplus in the presence of the citramalate pathway. Our study illustrates the application of metabolomics in identification of factors that alter cellular physiology for improvement of 1-propanol bioproduction.

Keywords: 1-Propanol; Escherichia coli; Mass spectrometry; Metabolic profiling; Metabolic turnover analysis; Synergy

References

  1. Metab Eng. 2013 May;17:12-22 - PubMed
  2. Metab Eng. 2017 May;41:135-143 - PubMed
  3. Anal Chem. 2009 Apr 15;81(8):3079-86 - PubMed
  4. Anal Chem. 2013 May 21;85(10):5191-9 - PubMed
  5. Metab Eng. 2008 Nov;10(6):305-11 - PubMed
  6. Aging Cell. 2010 Aug;9(4):616-25 - PubMed
  7. BMC Bioinformatics. 2011 May 04;12:131 - PubMed
  8. Microb Cell Fact. 2011 Jan 10;10(1):2 - PubMed
  9. Microb Cell Fact. 2015 May 28;14:73 - PubMed
  10. J Exp Bot. 2010 Feb;61(4):1041-51 - PubMed
  11. Anal Chem. 2010 Jun 1;82(11):4403-12 - PubMed
  12. Biotechnol Biofuels. 2015 Sep 15;8:144 - PubMed
  13. J Biosci Bioeng. 2017 Nov;124(5):498-505 - PubMed
  14. Appl Environ Microbiol. 2008 Dec;74(24):7802-8 - PubMed
  15. Biotechnol Bioeng. 1996 Oct 5;52(1):129-40 - PubMed
  16. Metab Eng. 2012 Sep;14(5):477-86 - PubMed
  17. Biotechnol Bioeng. 2012 Jun;109(6):1538-50 - PubMed
  18. J Biosci Bioeng. 2012 May;113(5):665-73 - PubMed
  19. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 - PubMed
  20. Appl Microbiol Biotechnol. 2008 Nov;81(1):89-98 - PubMed
  21. J Biosci Bioeng. 2014 Sep;118(3):350-5 - PubMed
  22. J Biosci Bioeng. 2008 Mar;105(3):249-60 - PubMed
  23. Trends Biotechnol. 2012 Oct;30(10):538-45 - PubMed
  24. Metab Eng. 2008 Sep;10(5):255-66 - PubMed
  25. Metabolomics. 2016;12:26 - PubMed
  26. Bioorg Med Chem. 1999 Oct;7(10):2209-13 - PubMed
  27. Metab Eng. 2016 Mar;34:88-96 - PubMed
  28. J Biol Chem. 1982 Dec 10;257(23):14526-37 - PubMed
  29. Metab Eng. 2008 Nov;10(6):312-20 - PubMed
  30. ACS Synth Biol. 2013 Mar 15;2(3):126-35 - PubMed
  31. J Bacteriol. 1992 Dec;174(23):7527-32 - PubMed
  32. Biotechnol Bioeng. 2015 Oct;112(10):2195-9 - PubMed

Substances

MeSH terms

Publication Types

Grant support