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Metabolic Engineering

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Biotechnology for the Future

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 100))

Abstract

Metabolic engineering is a powerful methodology aimed at intelligently designing new biological pathways, systems, and ultimately phenotypes through the use of recombinant DNA technology. Built largely on the theoretical and computational analysis of chemical systems, the field has evolved to incorporate a growing number of genome scale experimental tools. This combination of rigorous analysis and quantitative molecular biology methods has endowed metabolic engineering with an effective synergism that crosses traditional disciplinary bounds. As such, there are a growing number of applications for the effective employment of metabolic engineering, ranging from the initial industrial fermentation applications to more recent medical diagnosis applications. In this review we highlight many of the contributions metabolic engineering has provided through its history, as well as give an overview of new tools and applications that promise to have a large impact on the field's future.

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References

  1. Stephanopoulos G (1999) Metabolic fluxes and metabolic engineering. Metab Eng 1:1–11

    Article  CAS  Google Scholar 

  2. Stephanopoulos G, Vallino JJ (1991) Network rigidity and metabolic engineering in metabolite overproduction. Science 252:1675–1681

    Article  CAS  Google Scholar 

  3. Bailey JE (1991) Toward a Science of Metabolic Engineering. Science 252:1668–1675

    Article  CAS  Google Scholar 

  4. Sudesh K, Taguchi K, Doi Y (2002) Effect of increased PHA synthase activity on polyhydroxyalkanoates biosynthesis in Synechocystis sp PCC 6803. Int J Bio Macromol 30

    Google Scholar 

  5. Niederberger P, Prasad R, Miozzari G, Kacser H (1992) A strategy for increasing an in vivo flux by genetic manipulations. The tryptophan system of yeast. Biochem J 287:473–479

    CAS  Google Scholar 

  6. Farmer WR, Liao JC (2000) Improving lycopene production in Escherichia coli by engineering metabolic control. Nat Biotechnol 18:533–537

    Article  CAS  Google Scholar 

  7. Lu JL, Liao TC (1997) Metabolic engineering and control analysis for production of aromatics: Role of transaldolase. Biotechnol Bioeng 53:132–138

    Article  CAS  Google Scholar 

  8. Ostergaard S, Olsson L, Johnston M, Nielsen J (2000) Increasing galactose consumption by Saccharomyces cerevisiae through metabolic engineering of the GAL gene regulatory network. Nat Biotechnol 18:1283–1286

    Article  CAS  Google Scholar 

  9. Aiba S, Matsuoka M (1979) Identification of metabolic model: Citrate production from glucose by Candida lipolytica. Biotechnol Bioeng 21:1373–1386

    Article  CAS  Google Scholar 

  10. Stafford D, Yanagimachi K, Stephanopoulos G (2001) Metabolic engineering of indene bioconversion in Rhodococcus sp. Adv Biochem Eng Biotechnol 73:85–101

    CAS  Google Scholar 

  11. Ohta K, Beall DS, Mejia JP, Shanmugam KT, Ingram LO (1991) Metabolic Engineering of Klebsiella-Oxytoca M5a1 for Ethanol-Production from Xylose, Glucose. Appl Env Microbiol 57:2810–2815

    CAS  Google Scholar 

  12. van Maris AJA, Konings WN, van Dijken JP, Pronk JT (2004) Microbial export of lactic and 3-hydroxypropanoic acid: implications for industrial fermentation processes. Metab Eng 6:245–255

    Article  Google Scholar 

  13. Koffas MAG, Jung GY, Aon JC, Stephanopoulos G (2002) Effect of pyruvate carboxylase overexpression on the physiology of Corynebacterium glutamicum. Appl Env Microbiol 68:5422–5428

    Article  CAS  Google Scholar 

  14. Koffas MAG, Jung GY, Stephanopoulos G (2003) Engineering metabolism and product formation in Corynebacterium glutamicum by coordinated gene overexpression. Metab Eng 5:32–41

    Article  CAS  Google Scholar 

  15. Tong IT, Liao HH, Cameron DC (1991) 1,3-Propanediol production by Escherichia-coli expressing genes from the klebsiella-pneumoniae-dha regulon. Appl Env Microbiol 57:3541–3546

    CAS  Google Scholar 

  16. Vives J, Juanola S, Cairo JJ, Godia F (2003) Metabolic engineering of apoptosis in cultured animal cells: implications for the biotechnology industry. Metab Eng 5:124–132

    Article  CAS  Google Scholar 

  17. Cameron DC, Altaras NE, Hoffman ML, Shaw AJ (1998) Metabolic engineering of propanediol pathways. Biotechnol Progr 14:116–125

    Article  CAS  Google Scholar 

  18. Danner H, Braun R (1999) Biotechnology for the production of commodity chemicals from biomass. Chem Soc Rev 28:395–405

    Article  CAS  Google Scholar 

  19. Buckland BC et al. (1999) Microbial conversion of indene to indandiol: a key intermediate in the synthesis of CRIXIVAN. Metab Eng 1:63–74

    Article  CAS  Google Scholar 

  20. Stafford DE et al. (2002) Optimizing bioconversion pathways through systems analysis and metabolic engineering. Proc Natl Acad Sci USA 99:1801–1806

    Article  CAS  Google Scholar 

  21. Hood EE, Woodard SL, Horn ME (2002) Monoclonal antibody manufacturing in transgenic plants – myths and realities. Curr Opin Biotechnol 13:630–635

    Article  CAS  Google Scholar 

  22. Larrick J, Yu L, Naftzger C, Jaiswal S, Wyco K (2002) In: Hood E, Howard J (eds.) Plants as factories for protein production. Kluwer Academic, Boston. pp. 79–101

    Google Scholar 

  23. Morrow KJ (2002) Economics of antibody production – Various options available for large-scale bioprocessing. Genet Eng News 22:1–39

    Google Scholar 

  24. Nikolov Z, Hammes D (2002) In: Hood E, Howard J (eds) Plants as factories for protein production. Kluwer Academic, Boston. pp. 159–174

    Google Scholar 

  25. Thiel KA (2004) Biomanufacturing, from bust to boom…to bubble? Nat Biotechnol 22:1365–1372

    Article  CAS  Google Scholar 

  26. Stephanopoulos G (2000) Bioinformatics, metabolic engineering. Metabol Eng 2:157–158

    Article  Google Scholar 

  27. Lavoisier AL, DeLaplace PS (1994) Memoir on heat. Obes Res 2:189–203

    CAS  Google Scholar 

  28. Wang F, Raab RM, Washabaugh MW, Buckland BC (2000) Gene therapy, metabolic engineering. Metab Eng 2:126–139

    Article  CAS  Google Scholar 

  29. Keasling JD (1999) Gene-expression tools for the metabolic engineering of bacteria. Trends Biotechnol 17:452–460

    Article  CAS  Google Scholar 

  30. Goryshin IY, Jendrisak J, Hoffman LM, Meis R, Reznikoff WS (2000) Insertional transposon mutagenesis by electroporation of released Tn5 transposition complexes. Nat Biotechnol 18:97–100

    Article  CAS  Google Scholar 

  31. Tobin MB, Gustafsson C, Huisman GW (2000) Directed evolution: the ‘rational’ basis for ‘irrational’ design. Curr Opin Struc Biol 10:421–427

    Article  CAS  Google Scholar 

  32. Park SM, Klapa MI, Sinskey AJ, Stephanopoulos G (1999) Metabolite and isotopomer balancing in the analysis of metabolic cycles: II. Applications. Biotechnol Bioeng 62:392–401

    Article  CAS  Google Scholar 

  33. Klapa MI, Park SM, Sinskey AJ, Stephanopoulos G (1999) Metabolite and isotopomer balancing in the analysis of metabolic cycles: I. Theory. Biotechnol Bioeng 62:375–391

    Article  CAS  Google Scholar 

  34. Klapa MI, Aon JC, Stephanopoulos G (2003) Systematic quantification of complex metabolic flux networks using stable isotopes and mass spectrometry. Eur J Biochem 270:3525–3542

    Article  CAS  Google Scholar 

  35. Price ND, Papin JA, Schilling CH, Palsson BO (2003) Genome-scale microbial in silico models: the constraints-based approach. Trends Biotechnol 21:162–169

    Article  CAS  Google Scholar 

  36. Edwards JS, Ibarra RU, Palsson BO (2001) In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat Biotechnol 19:125–130

    Article  CAS  Google Scholar 

  37. Fell D (1997) Understanding the control of metabolism. Portland, Brookfield, VT

    Google Scholar 

  38. Stephanopoulos G, Aristidou AA, Nielsen J (1998) Metabolic engineering: principles, methodologies. Academic, San Diego

    Google Scholar 

  39. Nielsen J (2003) It is all about metabolic fluxes. J Bacteriol 185:7031–7035

    Article  CAS  Google Scholar 

  40. Gill RT, Wildt S, Yang YT, Ziesman S, Stephanopoulos G (2002) Genome wide screening for trait conferring genes using DNA micro-arrays. P Natl Acad Sci USA 99:7033

    Article  CAS  Google Scholar 

  41. Raab RM, Stephanopoulos G(2004) Dynamics of gene silencing by RNA interference. Biotechnol Bioeng 88:121–132

    Article  CAS  Google Scholar 

  42. Ashrafi K et al. (2003) Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421:268–272

    Article  CAS  Google Scholar 

  43. Chan C, Hwang D, Stephanopoulos GN, Yarmush ML, Stephanopoulos G (2003) Application of multivariate analysis to optimize function of cultured hepatocytes. Biotechnol Progr 19:580–598

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical Engineering, Room 56-459, Massachusetts Institute of Technology, 02139, Cambridge, MA, USA

    R. Michael Raab, Keith Tyo & Gregory Stephanopoulos

Authors
  1. R. Michael Raab
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  2. Keith Tyo
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  3. Gregory Stephanopoulos
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Correspondence to Gregory Stephanopoulos .

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J. Nielsen

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Raab, R.M., Tyo, K., Stephanopoulos, G. Metabolic Engineering. In: Nielsen, J. (eds) Biotechnology for the Future. Advances in Biochemical Engineering/Biotechnology, vol 100. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b136411

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