Skip to main content
Log in

Microbial Production of Fatty Acid via Metabolic Engineering and Synthetic Biology

  • Review Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

The microbial production of free fatty acids (FFAs) has gained great attention from the scientific community due to its significant environmental and economic benefits. FFAs can also be used as precursors for the production of valuable products, polymer additives and industrial chemicals by various biological or chemical reactions. Since microorganisms synthesize fatty acids (FAs) which are mainly used to form lipids for cell membrane constitution, FFAs are not normally accumulated as metabolic intermediates. FA metabolism is tightly regulated at transcriptional and post-transcriptional levels by both the transcription factor and product inhibition, meaning that FA overproduction may require extensive re-engineering of cellular metabolism. Therefore, we here present the recent efforts applied to enhance FFA production via metabolic engineering and synthetic biology with special reference to Escherichia coli.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Lennen, R. M. and B. F. Pfleger (2012) Engineering Escherichia coli to synthesize free fatty acids. Trends Biotechnol. 30: 659–667.

    Article  CAS  PubMed  Google Scholar 

  2. Cao, Y. X., W. H. Xiao, J. L. Zhang, Z. X. Xie, M. Z. Ding, and Y.J. Yuan (2016) Heterologous biosynthesis and manipulation of alkanes in Escherichia coli. Metab. Eng. 38: 19–28.

    Article  CAS  PubMed  Google Scholar 

  3. Choi, Y. J. and S. Y. Lee (2013) Microbial production of shortchain alkanes. Nature 502: 571–574.

    Article  CAS  PubMed  Google Scholar 

  4. Clomburg, J. M., M. D. Blankschien, J. E. Vick, A. Chou, S. Kim, and R. Gonzalez (2015) Integrated engineering of β-oxidation reversal and ω-oxidation pathways for the synthesis of medium chain ω-functionalized carboxylic acids. Metab. Eng. 28: 202–212.

    Article  CAS  PubMed  Google Scholar 

  5. Sudheer, P. D. V. N., J. Yun, S. Chauhan, J. Kang, and K. Y. Choi (2017) Screening, expression, and characterization of Baeyer-Villiger monooxygenases for the production of 9-(nonanoyloxy)nonanoic acid from oleic acid. Biotechnol. Bioprocess Eng. 22: 717–724.

    Article  CAS  Google Scholar 

  6. Lennen, R. M. and B. F. Pfleger (2013) Microbial production of fatty acid-derived fuels and chemicals. Curr. Opin. Biotechnol. 24: 1044–1053.

    Article  CAS  PubMed  Google Scholar 

  7. Do, K. H., H. M. Park, S. K. Kim, and H. S. Yun (2018) Production of cis-vaccenic acid-oriented unsaturated fatty acid in Escherichia coli. Biotechnol. Bioprocess Eng. 23: 100–107.

    Article  CAS  Google Scholar 

  8. Sherkhanov, S., T. P. Korman, S. G. Clarke, and J. U. Bowie (2016) Production of FAME biodiesel in E. coli by direct methylation with an insect enzyme. Sci. Rep. 6: 24239. doi: https://doi.org/10.1038/srep24239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Demirbas, A (2009) Progress and recent trends in biodiesel fuels. Energy Convers. Manag. 50: 14–34.

    Article  CAS  Google Scholar 

  10. Janßen, H. and A. Steinbüchel (2014) Fatty acid synthesis in Escherichia coli and its applications towards the production of fatty acid based biofuels. Biotechnol. Biofuels 7: 7. doi: https://doi.org/10.1186/1754-6834-7-7

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wu, L. F., P. C. Chen, A. P. Huang, and C. M. Lee (2012) The feasibility of biodiesel production by microalgae using industrial wastewater. Bioresour. Technol. 113: 14–18.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, F., L. H. Cheng, W. L. Gao, X. H. Xu, L. Zhang, and H. L. Chen (2011) Mechanism of lipid extraction from Botryococcus braunii FACHB 357 in a biphasic bioreactor. J. Biotechnol. 154: 281–284.

    Article  CAS  PubMed  Google Scholar 

  13. Almeida, J. R. M., L. C. L. Fávaro, and B. F. Quirino (2012) Biodiesel biorefinery: opportunities and challenges for microbial production of fuels and chemicals from glycerol waste. Biotechnol. Biofuels 5: 48. doi: https://doi.org/10.1186/1754-6834-5-48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ye, J., Y. Sha, Y. Zhang, Y. Yuan, and H. Wu (2011) Glycerol extracting dealcoholization for the biodiesel separation process. Bioresour. Technol. 102: 4759–4765.

    Article  CAS  PubMed  Google Scholar 

  15. Rahman, Z., N. Rashid, J. Nawab, M. Ilyas, B. H. Sung, and S. C. Kim (2016) Escherichia coli as a fatty acid and biodiesel factory: current challenges and future directions. Environ. Sci. Pollut. Res. 23: 12007–12018.

    Article  CAS  Google Scholar 

  16. Seo, E.-J., Y. J. Yeon, J.-H. Seo, J.-H. Lee, J. P. Boñgol, Y. Oh, J. M. Park, S.-M. Lim, C.-G. Lee, and J.-B. Park (2018) Enzyme/whole-cell biotransformation of plant oils, yeast derived oils, and microalgae fatty acid methyl esters into nnonanoic acid, 9-hydroxynonanoic acid, and 1,9-nonanedioic acid. Bioresour. Technol. 251: 288–294.

    Article  CAS  PubMed  Google Scholar 

  17. Jeon, E.-Y., J.-H. Seo, W.-R. Kang, M.-J. Kim, J.-H. Lee, D.-K. Oh, and J.-B. Park (2016) Simultaneous enzyme/wholecell biotransformation of plant oils into C9 carboxylic acids. ACS Catal. 6: 7547–7553.

    Article  CAS  Google Scholar 

  18. Ghim, C. M., T. Kim, R. J. Mitchell, and S. K. Lee (2010) Synthetic biology for biofuels: building designer microbes from the scratch. Biotechnol. Bioprocess Eng. 15: 11–21.

    Article  CAS  Google Scholar 

  19. Lennen, R. M. and B. F. Pfleger (2013) Modulating membrane composition alters free fatty acid tolerance in Escherichia coli. PLoS One 8: e54031. doi: https://doi.org/10.1002/gps.504710.1371/journal.pone.0054031

    Article  Google Scholar 

  20. Sherkhanov, S., T. P. Korman, and J. U. Bowie (2014) Improving the tolerance of Escherichia coli to medium-chain fatty acid production. Metab. Eng. 25: 1–7.

    Article  CAS  PubMed  Google Scholar 

  21. Schumacher, S. D. and J. Jose (2012) Expression of active human P450 3A4 on the cell surface of Escherichia coli by autodisplay. J. Biotechnol. 161: 113–120.

    Article  CAS  PubMed  Google Scholar 

  22. Handke, P., S. A. Lynch, and R. T. Gill (2011) Application and engineering of fatty acid biosynthesis in Escherichia coli for advanced fuels and chemicals. Metab. Eng. 13: 28–37. doi: https://doi.org/10.1016/j.ymben.2010.10.007

    Article  CAS  PubMed  Google Scholar 

  23. Pfleger, B. F., M. Gossing, and J. Nielsen (2015) Metabolic engineering strategies for microbial synthesis of oleochemicals. Metab. Eng. 29: 1–11.

    Article  CAS  PubMed  Google Scholar 

  24. Guchhait R. B., S. E. Polakis, P. Dimroth, E. Stoll, and J. L. M. Moss (1974) Acetyl coenzyme A carboxylase system of Escherichia coli: purification and properties of the biotin carboxylase, carboxyltransferase, and carboxyl carrier protein components. J. Biol. Chem 249: 6633–6645.

    Article  CAS  PubMed  Google Scholar 

  25. Cronan, J. E. and G. L. Waldrop (2002) Multi-subunit acetyl-CoA carboxylases. Prog. Lipid Res. 41: 407–435.

    Article  CAS  PubMed  Google Scholar 

  26. Lai, C. Y. and J. E. Cronan (2003) β-ketoacyl-acyl carrier protein synthase III (FabH) is essential for bacterial fatty acid synthesis. J. Biol. Chem. 278: 51494–51503.

    Article  CAS  PubMed  Google Scholar 

  27. Bergler, H., S. Fuchsbichler, G. Högenauer, and F. Turnowsky (1996) The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA. Eur. J. Biochem. 242: 689–694.

    Article  CAS  PubMed  Google Scholar 

  28. Feng, Y. and J. E. Cronan (2009) Escherichia coli unsaturated fatty acid synthesis. J. Biol. Chem. 284: 29526–29535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kass, L. R. and K. Bloch (1967) On the enzymatic synthesis of unsaturated fatty acids in Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 58: 1168–1173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fujita, Y., H. Matsuoka, and K. Hirooka (2007) Regulation of fatty acid metabolism in bacteria. Mol. Microbiol. 66: 829–839.

    Article  CAS  PubMed  Google Scholar 

  31. Simons, R. W., P. A. Egan, H. T. Chute, and W. D. Nunn (1980) Regulation of fatty acid degradation in Escherichia coli: isolation and characterization of strains bearing insertion and temperature-sensitive mutations in gene fadR. J. Bacteriol. 142: 621–632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. My, L., N. G. Achkar, J. P. Viala, and E. Bouveret (2015) Reassessment of the genetic regulation of fatty acid synthesis in Escherichia coli: global positive control by the dual functional regulator FadR. J. Bacteriol. 197: 1862–1872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu, Y., R. J. Heath, Z. Li, C. O. Rock, and S. W. White (2001) The FadR·DNA complex. J. Biol. Chem. 276: 17373–17379.

    Article  CAS  PubMed  Google Scholar 

  34. Cronan, J. E. (1997) In vivo evidence that acyl coenzyme A regulates DNA binding by the Escherichia coli FadR global transcription factor. J. Bacteriol. 179: 1819–1823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang, F., M. Ouellet, T. S. Batth, P. D. Adams, C. J. Petzold, A. Mukhopadhyay, and J. D. Keasling (2012) Enhancing fatty acid production by the expression of the regulatory transcription factor FadR. Metab. Eng. 14: 653–660.

    Article  CAS  PubMed  Google Scholar 

  36. Iram, S. H. and J. E. Cronan (2005) Unexpected functional diversity among FadR fatty acid transcriptional regulatory proteins. J. Biol. Chem. 280: 32148–32156.

    Article  CAS  PubMed  Google Scholar 

  37. He, L., Y. Xiao, N. Gebreselassie, F. Zhang, M. R. Antoniewiez, Y. J. Tang, and L. Peng (2014) Central metabolic responses to the overproduction of fatty acids in Escherichia coli based on 13C-metabolic flux analysis. Biotechnol. Bioeng. 111: 575–585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Farewell, A., A. A. Diez, C. C. DiRusso, and T. Nyström (1996) Role of the Escherichia coli FadR regulator in stasis survival and growth phase-dependent expression of the uspA, fad, and fab genes. J. Bacteriol. 178: 6443–6450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gui, L., A. Sunnarborg, and D. C. Laporte (1996) Regulated expression of a repressor protein: FadR activates iclR. J. Bacteriol. 178: 4704–4709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kornberg, H. L. (1966) The role and control of the glyoxylate cycle in Escherichia coli. Biochem. J. 99: 1–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Iram, S. H., and J. E. Cronan (2006) The β-oxidation systems of Escherichia coli and Salmonella enterica are not functionally equivalent. J. Bacteriol. 188: 599–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Campbell, J. W., R. M. Morgan-Kiss, and J. E. Cronan (2003) A new Escherichia coli metabolic competency: growth on fatty acids by a novel anaerobic β-oxidation pathway. Mol. Microbiol. 47: 793–805.

    Article  CAS  PubMed  Google Scholar 

  43. Cho, B. K., E. M. Knight, and B. Ø. Palsson (2006) Transcriptional regulation of the fad regulon genes of Escherichia coli by ArcA. Microbiology 152: 2207–2219.

    Article  CAS  PubMed  Google Scholar 

  44. Zhang, Y. M., H. Marrakchi, and C. O. Rock (2002) The FabR (YijC) Transcription factor regulates unsaturated fatty acid biosynthesis in Escherichia coli. J. Biol. Chem. 277: 15558–15565.

    Article  CAS  PubMed  Google Scholar 

  45. Zhu, K., Y. M. Zhang, and C. O. Rock (2009) Transcriptional regulation of membrane lipid homeostasis in Escherichia coli. J. Biol. Chem. 284: 34880–34888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Feng, Y., and J. E. Cronan (2011) Complex binding of the FabR repressor of bacterial unsaturated fatty acid biosynthesis to its cognate promoters. Mol. Microbiol. 80: 195–218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li, S. J. and J. E. Cronan (1993) Growth rate regulation of Escherichia coli acetyl coenzyme A carboxylase, which catalyzes the first committed step of lipid biosynthesis. J. Bacteriol. 175: 332–340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. James, E. S. and J. E. Cronan (2004) Expression of two Escherichia coli acetyl-CoA carboxylase subunits is autoregulated. J. Biol. Chem. 279: 2520–2527.

    Article  CAS  PubMed  Google Scholar 

  49. Meades, G., B. K. Benson, A. Grove, and G. L. Waldrop (2010) A tale of two functions: enzymatic activity and translational repression by carboxyltransferase. Nucleic Acids Res. 38: 1217–1227.

    Article  CAS  PubMed  Google Scholar 

  50. Yao, Z., R. M. Davis, R. Kishony, D. Kahne, and N. Ruiz (2012) Regulation of cell size in response to nutrient availability by fatty acid biosynthesis in Escherichia coli. Proc. Natl. Acad. Sci. 109: e2561–E2568. doi: https://doi.org/10.1073/pnas.1209742109

    Article  Google Scholar 

  51. Gerhardt, E. C. M., T. E. Rodrigues, M. Müller-Santos, F. O. Pedrosa, E. M. Souza, K. Forchhammer, and L. F. Huergo (2015) The Bacterial signal transduction protein GlnB regulates the committed step in fatty acid biosynthesis by acting as a dissociable regulatory subunit of acetyl-CoA carboxylase. Mol. Microbiol. 95: 1025–1035.

    Article  CAS  PubMed  Google Scholar 

  52. van Heeswijk, W. C., H. V. Westerhoff, and F. C. Boogerd (2013) Nitrogen assimilation in Escherichia coli: putting molecular data into a systems perspective. Microbiol. Mol. Biol. Rev. 77: 628–695.

    Article  PubMed  PubMed Central  Google Scholar 

  53. My, L., B. Rekoske, J. J. Lemke, J. P. Viala, R. L. Gourse, and E. Bouveret (2013) Transcription of the Escherichia coli fatty acid synthesis operon fabHDG is directly activated by FadR and inhibited by ppGpp. J. Bacteriol. 195: 3784–3795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Podkovyrov, S. and T. J. Larson (1995) Lipid biosynthetic genes and a ribosomal protein gene are cotranscribed. FEBS Lett. 368: 429–431.

    Article  CAS  PubMed  Google Scholar 

  55. Podkovyrov, S. M. and T. J. Larson (1996) Identification of promoter and stringent regulation of transcription of the fabH, fabD and fabG genes encoding fatty acid biosynthetic enzymes of Escherichia coli. Nucleic Acids Res. 24: 1747–1752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Durfee, T., A. M. Hansen, H. Zhi, F. R. Blattner, and D. J. Jin (2008) Transcription profiling of the stringent response in Escherichia coli. J. Bacteriol. 190: 1084–1096.

    Article  CAS  PubMed  Google Scholar 

  57. Heath, R. J., and C. O. Rock (1995) Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J. Biol. Chem. 270: 26538–26542.

    Article  CAS  PubMed  Google Scholar 

  58. Lee, S., S. Lee, Y. J. Yoon, and J. Lee (2013) Enhancement of long-chain fatty acid production in Escherichia coli by coexpressing genes, including fabF, involved in the elongation cycle of fatty acid biosynthesis. Appl. Biochem. Biotechnol. 169: 462–476.

    Article  CAS  PubMed  Google Scholar 

  59. Jeon, E., S. Lee, S. Lee, S. O. Han, Y. J. Yoon, and J. Lee (2012) Improved production of long-chain fatty acid in Escherichia coli by an engineering elongation cycle during fatty acid synthesis (FAS) through genetic manipulation. J. Microbiol. Biotechnol. 22: 990–999.

    Article  CAS  PubMed  Google Scholar 

  60. Edwards, P., J. S. Nelsen, J. G. Metz, and K. Dehesh (1997) Cloning of the fabF gene in an expression vector and in vitro characterization of recombinant fabF and fabB encoded enzymes from Escherichia coli. FEBS Lett. 402: 62–66.

    Article  CAS  PubMed  Google Scholar 

  61. Garwin, J. L., A. L. Klages, and J. E. Cronan (1980) Betaketoacyl-acyl carrier protein synthase II of Escherichia coli. Evidence for function in the thermal regulation of fatty acid synthesis. J. Biol. Chem. 255: 3263–3265.

    Article  CAS  PubMed  Google Scholar 

  62. Mejia, R., M. C. Gómez-Eichelmann, and M. S. Fernandez (1999) Fatty acid profile of Escherichia coli during the heatshock response. Biochem. Mol. Biol. Int. 47: 835–844.

    CAS  PubMed  Google Scholar 

  63. Heath, R. J. and C. O. Rock (1995) Regulation of malonyl-CoA metabolism by acyl-acyl carrier protein and beta-ketoacyl-acyl carrier protein synthases in Escherichia coli. J. Biol. Chem. 270: 15531–15538.

    Article  CAS  PubMed  Google Scholar 

  64. Davis, M. S. and J. E. Cronan (2001) Inhibition of Escherichia coli acetyl coenzyme A carboxylase by acyl-acyl carrier protein. J. Bacteriol. 183: 1499–1503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Heath, R. J. and C. O. Rock (1996) Inhibition of beta-ketoacylacyl carrier protein synthase III (FabH) by acyl-acyl carrier protein in Escherichia coli. J. Biol. Chem. 271: 10996–11000.

    Article  CAS  PubMed  Google Scholar 

  66. Joshi, V. C. and S. J. Wakil (1971) Studies on the mechanism of fatty acid synthesis: XXVI. Purification and properties of malonyl-coenzyme A—Acyl carrier protein transacylase of Escherichia coli. Arch. Biochem. Biophys. 143: 493–505.

    Article  CAS  PubMed  Google Scholar 

  67. Joshi, V. C. (1972) Mechanism of malonyl-coenzyme A-acylcarrier protein transacylase. Biochem. J. 128: 43–44.

    Article  Google Scholar 

  68. Heath, R. J. and C. O. Rock (1996) Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein in Escherichia coli. J. Biol. Chem. 271: 1833–1836.

    Article  CAS  PubMed  Google Scholar 

  69. Davis, M. S., J. Solbiati, and J. E. Cronan (2000) Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli. J. Biol. Chem. 275: 28593–28598.

    Article  CAS  PubMed  Google Scholar 

  70. Lennen, R. M., D. J. Braden, R. M. West, J. A. Dumesic, and B. F. Pfleger (2010) A process for microbial hydrocarbon synthesis: overproduction of fatty acids in Escherichia coli and catalytic conversion to alkanes. Biotechnol. Bioeng. 106: 193–202.

    Article  CAS  PubMed  Google Scholar 

  71. Lu, X., H. Vora, and C. Khosla (2008) Overproduction of free fatty acids in E. coli: implications for biodiesel production. Metab. Eng. 10: 333–339.

    Article  CAS  PubMed  Google Scholar 

  72. Liu, D., Y. Xiao, B. S. Evans, and F. Zhang (2013) Negative feedback regulation of fatty acid production based on a malonyl-CoA sensor-actuator. ACS Synth. Biol. 4: 132–140.

    Article  Google Scholar 

  73. Shin, K. S. and S. K. Lee (2017) Introduction of an acetyl-CoA carboxylation bypass into Escherichia coli for enhanced free fatty acid production. Bioresour. Technol. 245: 1627–1633.

    Article  CAS  PubMed  Google Scholar 

  74. Zha, W., S. B. Rubin-Pitel, Z. Shao, and H. Zhao (2009) Improving cellular malonyl-CoA level in Escherichia coli via metabolic engineering. Metab. Eng. 11: 192–198.

    Article  CAS  PubMed  Google Scholar 

  75. Miyahisa, I., M. Kaneko, N. Funa, H. Kawasaki, H. Kojima, Y. Ohnishi, and S. Horinouchi (2005) Efficient production of (2S)-flavanones by Escherichia coli containing an artificial biosynthetic gene cluster. Appl. Microbiol. Biotechnol. 68: 498–504.

    Article  CAS  PubMed  Google Scholar 

  76. Leonard, E., K. H. Lim, P. N. Saw, and M. A. G. Koffas (2007) Engineering central metabolic pathways for high-level flavonoid production in Escherichia coli. Appl. Environ. Microbiol. 73: 3877–3886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhang, X., A. Agrawal, and K. Y. San (2012) Improving fatty acid production in Escherichia coli through the overexpression of malonyl-CoA-Acyl carrier protein transacylase. Biotechnol. Prog. 28: 60–65.

    Article  PubMed  Google Scholar 

  78. Lee, S., E. Jeon, H. S. Yun, and J. Lee (2011) Improvement of fatty acid biosynthesis by engineered recombinant Escherichia coli. Biotechnol. Bioprocess Eng. 16: 706–713.

    Article  CAS  Google Scholar 

  79. Tsay, J. T., W. Oh, T. J. Larson, S. Jackowski, and C. O. Rock (1992) Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J. Biol. Chem. 267: 6807–6814.

    Article  CAS  PubMed  Google Scholar 

  80. Abbadi, A., M. Brummel, and F. Spener (2000) Knockout of the regulatory site of 3-ketoacyl-ACP synthase III enhances shortand medium-chain acyl-ACP synthesis. Plant J. 24: 1–9.

    Article  CAS  PubMed  Google Scholar 

  81. Tseng, H. C. and K. L. J. Prather (2012) Controlled biosynthesis of odd-chain fuels and chemicals via engineered modular metabolic pathways. Proc. Natl. Acad. Sci. 109: 17925–17930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Torella, J. P., T. J. Ford, S. N. Kim, A. M. Chen, J. C. Way, and P. A. Silver (2013) Tailored fatty acid synthesis via dynamic control of fatty acid elongation. Proc. Natl. Acad. Sci. 110: 11290–11295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Choi, K. H., R. J. Heath, and C. O. Rock (2000) Beta-ketoacylacyl carrier protein synthase III (FabH) is a determining factor in branched-chain fatty acid biosynthesis. J. Bacteriol. 182: 365–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Haushalter, R. W., W. Kim, T. A. Chavkin, L. The, M. E. Garber, M. Nhan, P. D. Adams, C. J. Petzold, L. Katz, and J. D. Keasling (2014) Production of anteiso-branched fatty acids in Escherichia coli:next generation biofuels with improved cold-flow properties. Metab. Eng. 26: 111–118.

    Article  CAS  PubMed  Google Scholar 

  85. Jiang, W., Y. Jiang, G. J. Bentley, D. Liu, Y. Xiao, and F. Zhang (2015) Enhanced production of branched-chain fatty acids by replacing β-ketoacyl-(acyl-carrier-protein) synthase III (FabH). Biotechnol. Bioeng. 112: 1613–1622.

    Article  CAS  PubMed  Google Scholar 

  86. Heath, R. J. and C. O. Rock (1996) Roles of the FabA and FabZ beta-hydroxyacyl-acyl carrier protein dehydratases in Escherichia coli fatty acid biosynthesis. J. Biol. Chem. 271: 27795–27801.

    Article  CAS  PubMed  Google Scholar 

  87. Zeng, D., J. Zhao, H. S. Chung, Z. Guan, C. R. H. Raetz, and P. Zhou (2013) Mutants resistant to LpxC inhibitors by rebalancing cellular homeostasis. J. Biol. Chem. 288: 5475–5486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Silbert, D. F. and P. R. Vagelos (1967) Fatty acid mutant of E. coli lacking a beta-hydroxydecanoyl thioester dehydrase. Proc. Natl. Acad. Sci. USA 58: 1579–1586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Baba, T., T. Ara, M. Hasegawa, Y. Takai, Y. Okumura, M. Baba, K. A. Datsenko, M. Tomita, B. L. Wanner, and H. Mori (2006) Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2: 2006.0008. doi: https://doi.org/10.1038/msb4100050

    Article  PubMed Central  Google Scholar 

  90. Cronan, J. E., D. F. Silbert, D. L. Wulff, and D. L. Wulff (1972) Mapping of the fabA locus for unsaturated fatty acid biosynthesis in Escherichia coli. J. Bacteriol. 112: 206–211

    Article  PubMed  PubMed Central  Google Scholar 

  91. Cao, Y., J. Yang, M. Xian, X. Xu, and W. Liu (2010) Increasing unsaturated fatty acid contents in Escherichia coli by coexpression of three different genes. Appl. Microbiol. Biotechnol. 87: 271–280.

    Article  CAS  PubMed  Google Scholar 

  92. D’Agnolo, G., I. S. Rosenfeld, and P. R. Vagelos (1975) Multiple forms of beta-ketoacyl-acyl carrier protein synthetase in Escherichia coli. J. Biol. Chem. 250: 5289–5294.

    Article  PubMed  Google Scholar 

  93. Cronan, J. E., C. H. Birge, and P. R. Vagelos (1969) Evidence for two genes specifically involved in unsaturated fatty acid biosynthesis in Escherichia coli. J. Bacteriol. 100: 601–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lee, S., Y. Jung, S. Lee, and J. Lee (2013) Correlations between FAS elongation cycle genes expression and fatty acid production for improvement of long-chain fatty acids in Escherichia coli. Appl. Biochem. Biotechnol. 169: 1606–1619.

    Article  CAS  PubMed  Google Scholar 

  95. Kim, S., C. H. Lee, S. W. Nam, and P. Kim (2011) Alteration of reducing powers in an isogenic phosphoglucose isomerase (pgi)-disrupted Escherichia coli expressing NAD(P)-dependent malic enzymes and NADP-dependent glyceraldehyde 3-phosphate dehydrogenase. Lett. Appl. Microbiol. 52: 433–440.

    Article  CAS  PubMed  Google Scholar 

  96. Steen, E. J., Y. Kang, G. Bokinsky, Z. Hu, A. Schirmer, A. McClure, S. B. Del Cardayre, and J. D. Keasling (2010) Microbial production of fatty-acid-derived fuels and chemicals from plant biomass. Nature 463: 559–562.

    Article  CAS  PubMed  Google Scholar 

  97. Mazumdar, S., M. D. Blankschien, J. M. Clomburg, and R. Gonzalez (2013) Efficient synthesis of L-lactic acid from glycerol by metabolically engineered Escherichia coli. Microb. Cell Fact. 12: 7. doi: https://doi.org/10.1186/1475-2859-12-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Li, M., X. Zhang, A. Agrawal, and K. Y. San (2012) Effect of acetate formation pathway and long chain fatty acid CoA-ligase on the free fatty acid production in E. coli expressing acy-ACP thioesterase from Ricinus communis. Metab. Eng. 14: 380–387.

    Article  CAS  PubMed  Google Scholar 

  99. Zhang, X., M. Li, A. Agrawal, and K.-Y. San (2011) Efficient free fatty acid production in Escherichia coli using plant acyl-ACP thioesterases. Metab. Eng. 13: 713–722.

    Article  CAS  PubMed  Google Scholar 

  100. Clomburg, J. M., J. E. Vick, M. D. Blankschien, M. Rodríguez-Moyá, and R. Gonzalez (2012) A synthetic biology approach to engineer a functional reversal of the β-oxidation cycle. ACS Synth. Biol. 1: 541–554.

    Article  CAS  PubMed  Google Scholar 

  101. Wu, J., X. Zhang, X. Xia, and M. Dong (2017) A systematic optimization of medium chain fatty acid biosynthesis via the reverse beta-oxidation cycle in Escherichia coli. Metab. Eng. 41: 115–124.

    Article  PubMed  Google Scholar 

  102. Ranganathan, S., T. W. Tee, A. Chowdhury, A. R. Zomorrodi, J. M. Yoon, Y. Fu, J. V. Shanks, and C. D. Maranas (2012) An integrated computational and experimental study for overproducing fatty acids in Escherichia coli. Metab. Eng. 14: 687–704.

    Article  CAS  PubMed  Google Scholar 

  103. Soma, Y., K. Tsuruno, M. Wada, A. Yokota, and T. Hanai (2014) Metabolic flux redirection from a central metabolic pathway toward a synthetic pathway using a metabolic toggle switch. Metab. Eng. 23: 175–184.

    Article  CAS  PubMed  Google Scholar 

  104. Liu, H., C. Yu, D. Feng, T. Cheng, X. Meng, W. Liu, H. Zou, and M. Xian (2012) Production of extracellular fatty acid using engineered Escherichia coli. Microb. Cell Fact. 11: 41. doi: https://doi.org/10.1186/1475-2859-11-41

    Article  PubMed  PubMed Central  Google Scholar 

  105. Huang, Y. T., Y. C. Liaw, V. Y. Gorbatyuk, and T. H. Huang (2001) Backbone dynamics of Escherichia coli thioesterase/protease I: evidence of a flexible active-site environment for a serine protease1. J. Mol. Biol. 307: 1075–1090.

    Article  CAS  PubMed  Google Scholar 

  106. Lo, Y. C., S. C. Lin, J. F. Shaw, and Y. C. Liaw (2003) Crystal structure of Escherichia coli thioesterase I/protease I/lysophospholipase L1: consensus sequence blocks constitute the catalytic center of SGNH-hydrolases through a conserved hydrogen bond network. J. Mol. Biol. 330: 539–551.

    Article  CAS  PubMed  Google Scholar 

  107. Lee, L. C., Y. L. Chou, H. H. Chen, Y. L. Lee, and J. F. Shaw (2009) Functional role of a non-active site residue Trp23 on the enzyme activity of Escherichia coli thioesterase I/protease I/lysophospholipase L1. Biochim. Biophys. Acta-Proteins Proteomics 1794: 1467–1473.

  108. Lee, L. C., Y. L. Lee, R. J. Leu, and J. F. Shaw (2006) Functional role of catalytic triad and oxyanion hole-forming residues on enzyme activity of Escherichia coli thioesterase I/protease I/phospholipase L1. Biochem. J. 397: 69–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lo, Y. C., S. C. Lin, J. F. Shaw, and Y. C. Liaw (2005) Substrate specificities of Escherichia coli thioesterase I/protease I/lysophospholipase L1 are governed by its switch loop movement. Biochemistry 44: 1971–1979.

    Article  CAS  PubMed  Google Scholar 

  110. Barnes, E. M. and S. J. Wakil (1968) Studies on the mechanism of fatty acid synthesis. XIX. Preparation and general properties of palmityl thioesterase. J. Biol. Chem. 243: 2955–2962.

    CAS  PubMed  Google Scholar 

  111. Barnes, E. M. (1975) Long-chain fatty acyl thioesterases I and II from Escherichia coli. Methods Enzymol. 35: 102–109.

    Article  PubMed  Google Scholar 

  112. Cho, H. and J. E. Cronan (1993) Escherichia coli thioesterase I, molecular cloning and sequencing of the structural gene and identification as a periplasmic enzyme. J. Biol. Chem. 268: 9238–9245.

    Article  CAS  PubMed  Google Scholar 

  113. Cho, H. and J. E. Cronan (1995) Defective export of a periplasmic enzyme disrupts regulation of fatty acid synthesis. J. Biol. Chem. 270: 4216–4219.

    Article  CAS  PubMed  Google Scholar 

  114. Shin, K. S., S. Kim, and S. K. Lee (2016) Improvement of free fatty acid production using a mutant acyl-CoA thioesterase I with high specific activity in Escherichia coli. Biotechnol. Biofuels 9: 208. doi: https://doi.org/10.1186/s13068-016-0622-y

    Article  PubMed  PubMed Central  Google Scholar 

  115. Ohlrogge, J., L. Savage, J. Jaworski, T. Voelker, and D. Post-Beittenmiller (1995) Alteration of acyl-acyl carrier protein pools and acetyl-CoA carboxylase expression in Escherichia coli by a plant medium chain acyl-acyl carrier protein thioesterase. Arch. Biochem. Biophys. 317: 185–190

    Article  CAS  PubMed  Google Scholar 

  116. Lee, S., S. Park, C. Park, S. P. Pack, and J. Lee (2014) Enhanced free fatty acid production by codon-optimized Lactococcus lactis acyl-ACP thioesterase gene expression in Escherichia coli using crude glycerol. Enzyme Microb. Technol. 67: 8–16.

    Article  CAS  PubMed  Google Scholar 

  117. Lennen, R. M., M. A. Kruziki, K. Kumar, R. A. Zinkel, K. E. Burnum, M. S. Lipton, S. W. Hoover, D. R. Ranatunga, T. M. Wittkopp, W. D. Marner, et al (2011) Membrane stresses induced by overproduction of free fatty acids in Escherichia coli. Appl. Environ. Microbiol. 77: 8114–8128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Lennen, R. M., M. G. Politz, M. A. Kruziki, and B. F. Pfleger (2013) Identification of transport proteins involved in free fatty acid efflux in Escherichia coli. J. Bacteriol. 195: 135–144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Oh, H. Y., J. O. Lee, and O. B. Kim (2012) Increase of organic solvent tolerance of Escherichia coli by the deletion of two regulator genes, fadR and marR. Appl. Microbiol. Biotechnol. 96: 1619–1627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Dellomonaco, C., J. M. Clomburg, E. N. Miller, and R. Gonzalez (2011) Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals. Nature 476: 355–359.

    Article  CAS  PubMed  Google Scholar 

  121. Leonard, E., P. K. Ajikumar, K. Thayer, W. H. Xiao, J. D. Mo, B. Tidor, G. Stephanopoulos, and K. L. J. Prather (2010) Combining metabolic and protein engineering of a terpenoid biosynthetic pathway for overproduction and selectivity control. Proc. Natl. Acad. Sci. 107: 13654–13659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Xu, P., Q. Gu, W. Wang, L. Wong, A. G. W. Bower, C. H. Collins, and M. A. G. Koffas (2013) Modular optimization of multi-gene pathways for fatty acids production in E. coli. Nat. Commun. 4: 1409. doi: https://doi.org/10.1038/ncomms2425

    Article  PubMed  Google Scholar 

  123. Subrahmanyam, S. and J. E. Cronan (1998) Overproduction of a functional fatty acid biosynthetic enzyme blocks fatty acid synthesis in Escherichia coli. J. Bacteriol. 180: 4596–4602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Keating, D. H., M. R. Carey, and J. E. Cronan (1995) The unmodified (apo) form of Escherichia coli acyl carrier protein is a potent inhibitor of cell growth. J. Biol. Chem. 270: 22229–22235.

    Article  CAS  PubMed  Google Scholar 

  125. Yu, X., T. Liu, F. Zhu, and C. Khosla (2011) In vitro reconstitution and steady-state analysis of the fatty acid synthase from Escherichia coli. Proc. Natl. Acad. Sci. USA 108: 18643–18648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Tao, H., Y. Zhang, X. Cao, Z. Deng, and T. Liu (2016) Absolute quantification of proteins in the fatty acid biosynthetic pathway using protein standard absolute quantification. Synth. Syst. Biotechnol. 1: 150–157.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Xu, P., L. Li, F. Zhang, G. Stephanopoulos, and M. Koffas (2014) Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. Proc. Natl. Acad. Sci. USA 111: 11299–11304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. McKee, A. E., B. J. Rutherford, D. C. Chivian, E. K. Baidoo, D. Juminaga, D. Kuo, P. I. Benke, J. A. Dietrich, S. M. Ma, A. P. Arkin, C. J. Petzold, P. D. Adams, J. D. Keasling, and S. R. Chhabra (2012) Manipulation of the carbon storage regulator system for metabolite remodeling and biofuel production in Escherichia coli. Microb. Cell Fact. 11: 79. doi: https://doi.org/10.1186/1475-2859-11-79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Tee, T. W., A. Chowdhury, C. D. Maranas, and J. V. Shanks (2014) Systems metabolic engineering design: fatty acid production as an emerging case study. Biotechnol. Bioeng. 111: 849–857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. San, K. Y. and M. Li (2013) Genetically engineered bacteria and method for synthesizing fatty acids. US Patent WO 2013059218.

    Google Scholar 

  131. Jeon, E., S. Lee, S. Lee, S. O. Han, Y. J. Yoon, and J. Lee (2012) Improved production of long-chain fatty acid in Escherichia coli by an engineering elongation cycle during fatty acid synthesis (FAS) through genetic manipulation. J. Microbiol. Biotechnol. 22: 990–999.

    Article  CAS  PubMed  Google Scholar 

  132. Liu, D., N. Wan, F. Zhang, Y. J. Tang, and S. G. Wu (2017) Enhancing fatty acid production in Escherichia coli by Vitreoscilla hemoglobin overexpression. Biotechnol. Bioeng. 114: 463–467.

    Article  CAS  PubMed  Google Scholar 

  133. Charusanti, P., T. M. Conrad, E. M. Knight, K. Venkataraman, N. L. Fong, B. Xie, Y. Gao, and B. Ø. Palsson (2010) Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene. PLoS Genet. 6: e1001186. doi: https://doi.org/10.1371/journal.pgen.1001186

    Article  Google Scholar 

  134. Chemler, J. A., Z. L. Fowler, K. P. McHugh, and M. A. G. Koffas (2010) Improving NADPH availability for natural product biosynthesis in Escherichia coli by metabolic engineering. Metab. Eng. 12: 96–104.

    Article  CAS  PubMed  Google Scholar 

  135. Martínez, I., J. Zhu, H. Lin, G. N. Bennett, and K. Y. San (2008) Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways. Metab. Eng. 10: 352–359.

    Article  PubMed  Google Scholar 

  136. Ma, S. M., D. E. Garcia, A. M. Redding-Johanson, G. D. Friedland, R. Chan, T. S. Batth, J. R. Haliburton, D. Chivian, J. D. Keasling, C. J. Petzold, T. K. Lee, and S. R. Chhabra (2011) Optimization of a heterologous mevalonate pathway through the use of variant HMG-CoA reductases. Metab. Eng. 13: 588–597.

    Article  CAS  PubMed  Google Scholar 

  137. Bastian, S., X. Liu, J. T. Meyerowitz, C. D. Snow, M. M. Y. Chen, and F. H. Arnold (2011) Engineered ketol-acid reductoisomerase and alcohol dehydrogenase enable anaerobic 2-methylpropan-1-ol production at theoretical yield in Escherichia coli. Metab. Eng. 13: 345–352.

    Article  CAS  PubMed  Google Scholar 

  138. Nor'Aini, A. R., Y. Shirai, M. A. Hassan, and K. Shimizu (2006) Investigation on the metabolic regulation of pgi gene knockout Escherichia coli by enzyme activities and intracellular metabolite concentrations. Malaysian J. Microbiol. 2: 24–31.

    Google Scholar 

  139. Lim, S. J., Y. M. Jung, H. D. Shin, and Y. H. Lee (2002) Amplification of the NADPH-related genes zwf and gnd for the oddball biosynthesis of PHB in an E. coli transformant harboring a cloned phbCAB operon. J. Biosci. Bioeng. 93: 543–549.

    Article  CAS  PubMed  Google Scholar 

  140. Canonaco, F., T. A. Hess, S. Heri, T. Wang, T. Szyperski, and U. Sauer (2001) Metabolic flux response to phosphoglucose isomerase knock-out in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA. FEMS Microbiol. Lett. 204: 247–252.

    Article  CAS  PubMed  Google Scholar 

  141. Zhang, J., N. Sonnenschein, T. P. B. Pihl, K. R. Pedersen, M. K. Jensen, and J. D. Keasling (2016) Engineering an NADPH/NADP+ redox biosensor in yeast. ACS Synth. Biol. 5: 1546–1556.

    Article  CAS  PubMed  Google Scholar 

  142. Siedler, S., G. Schendzielorz, S. Binder, L. Eggeling, S. Bringer, and M. Bott (2014) SoxR as a single-cell biosensor for NADPH-consuming enzymes in Escherichia coli. ACS Synth. Biol. 3: 41–47.

    Article  CAS  PubMed  Google Scholar 

  143. Auriol, C., G. Bestel-Corre, J. B. Claude, P. Soucaille, and I. Meynial-Salles (2011) Stress-induced evolution of Escherichia coli points to original concepts in respiratory cofactor selectivity. Proc. Natl. Acad. Sci. USA 108: 1278–1283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Sauer, U., F. Canonaco, S. Heri, A. Perrenoud, and E. Fischer (2004) The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli. J. Biol. Chem. 279: 6613–6619.

    Article  CAS  PubMed  Google Scholar 

  145. Wu, H., M. Karanjikar, and K. Y. San (2014) Metabolic engineering of Escherichia coli for efficient free fatty acid production from glycerol. Metab. Eng. 25: 82–91.

    Article  CAS  PubMed  Google Scholar 

  146. Lee, H. C., J. S. Kim, W. Jang, and S. Y. Kim (2010) High NADPH/NADP+ ratio improves thymidine production by a metabolically engineered Escherichia coli strain. J. Biotechnol. 149: 24–32.

    Article  CAS  PubMed  Google Scholar 

  147. Javidpour, P., J. H. Pereira, E. B. Goh, R. P. McAndrew, S. M. Ma, G. D. Friedland, J. D. Keasling, S. R. Chhabra, P. D. Adams, and H. R. Beller (2014) Biochemical and structural studies of NADH-dependent FabG used to increase the bacterial production of fatty acids under anaerobic conditions. Appl. Environ. Microbiol. 80: 497–505.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Wu, J., X. Zhang, P. Zhou, J. Huang, X. Xia, W. Li, Z. Zhou, Y. Chen, Y. Liu, and M. Dong (2017) Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement. Metab. Eng. 44: 313–324.

    Article  CAS  PubMed  Google Scholar 

  149. Chan, D. I. and H. J. Vogel (2010) Current understanding of fatty acid biosynthesis and the acyl carrier protein. Biochem. J. 430: 1–19.

    Article  CAS  PubMed  Google Scholar 

  150. Rock, C. O., S. E. Goelz, and J. E. Cronan (1981) Phospholipid synthesis in Escherichia coli. Characteristics of fatty acid transfer from acyl-acyl carrier protein to sn-glycerol 3-phosphate. J. Biol. Chem. 256: 736–742.

    Article  CAS  PubMed  Google Scholar 

  151. Jarboe, L. R., L. A. Royce, and P. Liu (2013) Understanding biocatalyst inhibition by carboxylic acids. Front. Microbiol. 4: 272. doi: https://doi.org/10.3389/fmicb.2013.00272

    Article  PubMed  PubMed Central  Google Scholar 

  152. Woo, J. M., J. W. Kim, J. W. Song, L. M. Blank, and J. B. Park (2016) Activation of the glutamic acid-dependent acid resistance system in Escherichia coli BL21(DE3) leads to increase of the fatty acid biotransformation activity. PLoS One 11: e0163265. doi: https://doi.org/10.1371/journal.pone.0163265

    Article  Google Scholar 

  153. Seo, J. H., S. W. Baek, J. Lee, and J.B. Park (2017) Engineering Escherichia coli BL21 genome to improve the heptanoic acid tolerance by using CRISPR-Cas9 system. Biotechnol. Bioprocess Eng. 22: 231–238.

    Article  CAS  Google Scholar 

  154. Royce, L. A., J. M. Yoon, Y. Chen, E. Rickenbach, J. V. Shanks, and L. R. Jarboe (2015) Evolution for exogenous octanoic acid tolerance improves carboxylic acid production and membrane integrity. Metab. Eng. 29: 180–188.

    Article  CAS  PubMed  Google Scholar 

  155. Foo, J. and S. Leong (2013) Directed evolution of an E. coli inner membrane transporter for improved efflux of biofuel molecules. Biotechnol. Biofuels 6: 81. doi: https://doi.org/10.1186/1754-6834-6-81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Wu, J., Z. Wang, X. Zhang, P. Zhou, X. Xia, and M. Dong (2019) Improving medium chain fatty acid production in Escherichia coli by multiple transporter engineering. Food Chem. 272: 628–634.

    Article  CAS  PubMed  Google Scholar 

  157. Tan, Z., W. Black, J. M. Yoon, J. V. Shanks, and L. R. Jarboe (2017) Improving Escherichia coli membrane integrity and fatty acid production by expression tuning of FadL and OmpF. Microb. Cell Fact. 16: 38. doi: https://doi.org/10.1186/s12934-017-0650-8

    Article  PubMed  PubMed Central  Google Scholar 

  158. Tan, Z., P. Khakbaz, Y. Chen, J. Lombardo, J. M. Yoon, J. V. Shanks, J. B. Klauda, and L. R. Jarboe (2017) Engineering Escherichia coli membrane phospholipid head distribution improves tolerance and production of biorenewables. Metab. Eng. 44: 1–12.

    Article  CAS  PubMed  Google Scholar 

  159. Youngquist, J. T., M. H. Schumacher, J. P. Rose, T. C. Raines, M. C. Politz, M. F. Copeland, and B. F. Pfleger (2013) Production of medium chain length fatty alcohols from glucose in Escherichia coli. Metab. Eng. 20: 177–186.

    Article  CAS  PubMed  Google Scholar 

  160. Bremer, H. and P. P. Dennis (1996). Modulation of chemical composition and other parameters of the cell by growth rate. pp. 1553–1569. In: Neidhardt, F. C., R. Curtiss III, J. L. Ingraham, E. C. C. Lin, K. B. Low, B. Magasanik, W. S. Reznikoff, M. Riley, M. Schaechter, and H. E. Umbarger (eds.), Escherichia coli and Salmonella typhimurium: cellular and molecular biology. American Society for Microbiology Press, Washington, D.C.

    Google Scholar 

  161. Chubukov, V. and U. Sauer (2014) Environmental dependence of stationary-phase metabolism in Bacillus subtilis and Escherichia coli. Appl. Environ. Microbiol. 80: 2901–2909.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Peralta-Yahya, P. P., F. Zhang, S. B. del Cardayre, and J. D. Keasling (2012) Microbial engineering for the production of advanced biofuels. Nature 488: 320–328.

    Article  CAS  PubMed  Google Scholar 

  163. Liu, T., H. Vora, and C. Khosla (2010) Quantitative analysis and engineering of fatty acid biosynthesis in E. coli. Metab. Eng. 12: 378–386.

    Article  CAS  PubMed  Google Scholar 

  164. Zheng, Y., L. Li, Q. Liu, J. Yang, Y. Cao, X. Jiang, G. Zhao, M. Xian, and M. Xian (2012) Boosting the free fatty acid synthesis of Escherichia coli by expression of a cytosolic Acinetobacter baylyi thioesterase. Biotechnol. Biofuels 5: 76. doi: https://doi.org/10.1186/1754-6834-5-76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Lee, S., E. Jeon, Y. Jung, and J. Lee (2012) Heterologous coexpression of accA, fabD, and thioesterase genes for improving long-chain fatty acid production in Pseudomonas aeruginosa and Escherichia coli. Appl. Biochem. Biotechnol. 167: 24–38.

    Article  CAS  PubMed  Google Scholar 

  166. Zhang, F., J. M. Carothers, and J. D. Keasling (2012) Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids. Nat. Biotechnol. 30: 354–359.

    Article  CAS  PubMed  Google Scholar 

  167. Kim, S., J. M. Clomburg, and R. Gonzalez (2015) Synthesis of medium-chain length (C6–C10) fuels and chemicals via β-oxidation reversal in Escherichia coli. J. Ind. Microbiol. Biotechnol. 42: 465–475.

    Article  CAS  PubMed  Google Scholar 

  168. Tan, Z., J. M. Yoon, A. Chowdhury, K. Burdick, L. R. Jarboe, C. D. Maranas, and J. V. Shanks (2018) Engineering of E. coli inherent fatty acid biosynthesis capacity to increase octanoic acid production. Biotechnol. Biofuels 11: 87. doi: https://doi.org/10.1186/s13068-018-1078-z

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sung Kuk Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sathesh-Prabu, C., Shin, K.S., Kwak, G.H. et al. Microbial Production of Fatty Acid via Metabolic Engineering and Synthetic Biology. Biotechnol Bioproc E 24, 23–40 (2019). https://doi.org/10.1007/s12257-018-0374-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-018-0374-6

Keywords

Navigation