Progress in metabolic engineering

Current Opinion in Biotechnology

Volumn 7, Issue 2, 1996, Pages 198-204

  Farmer, William R ^a   Liao, James C ^a  

^a Texas AandM University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; AROMATIC AMINO ACID; ASPARTIC ACID; BUTYRIC ACID; XYLOSE;

AMINO ACID SYNTHESIS; ARABIDOPSIS; BACTERIAL METABOLISM; BIOENGINEERING; CORYNEBACTERIUM; ESCHERICHIA COLI; METABOLIC REGULATION; NONHUMAN; PRIORITY JOURNAL; REVIEW; ZYMOMONAS MOBILIS;

ARABIDOPSIS; ARABIDOPSIS THALIANA; BACTERIA (MICROORGANISMS); CORYNEBACTERIUM; ESCHERICHIA COLI; ZYMOMONAS MOBILIS;

EID: 0029935114     PISSN: 09581669     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0958-1669(96)80013-9     Document Type: Article

References (40)

1. Bailey JE: Toward a science of metabolic engineering. Science 1991, 282:1668-1675.
2. Cameron DC, Tong IT: Cellular and metabolic engineering: an overview. Appl Biochem Biotechnol 1993, 38:105-140.
3. Lee J, Goel A, Ataai MM, Domach MM: Flux adaptations of citrate synthase deficient Escherichia coli. Ann NY Acad Sci 1994, 745:35-50. This work attempts to determine the role of the TCA cycle in the metabolism of E. coli by knocking out the pathway connecting glycolysis to the TCA cycle. Glycolysis in the mutant is determined to provide an ATP yield comparable to the wild type. Modulation of acetate/formate production is hypothesized to be a key factor in ATP production in the mutant. Carbon dioxide is observed to increase the growth yield and the specific growth rate by some unknown mechanism.
4. Liao JC, Chao Y-P, Patnaik R: Alteration of the biochemical valves in the central metabolism of Escherichia coli. Ann NY Acad Sci 1994, 745:21-34.
5. Chao Y-P, Liao JC: Metabolic responses to substrate futile cycling in Escherichia coli. J Biol Chem 1994, 269:5122-5126. Simultaneous over-expression of PCK and PPC in E. coli stimulates respiration, glucose consumption, and the production of pyruvate and acetate. These observations are speculated to be cellular responses to substrate futile cycling; however, the detailed mechanisms involved are still unknown.
6. Dave E, Guest JR, Attwood MM Metabolic engineering in Escherichia coli: lowering the lipoyl domain content of the pyruvate dehydrogenase complex adversely affects the growth rate and yield. Microbiology 1995, 141:1839-1849. An E. coli mutant with PDH complex containing a lower lipoyl domain content exhibits a decrease in growth yield and maintenance energy on a variety of sugars. When pyruvate is the carbon source, the mutant growth yield is similar to the wild type. This leads to the interesting possibility that pyruvate lifts the repression of the transcription of the genes for the PDH complex. Thus, increased expression of the mutant PDH can compensate for its reduced activity.
7. Tsai PS, Kallio PT, Bailey JE: Fnr, a global transcriptional regulator of Escherichia coli, activates the Vitreoscilla hemoglobin (Vhb) promoter and intracellular Vhb expression increases cytochrome d promoter activity. Biotechnol Prog 1995, 11:288-293. The expression of Vhb in vivo is shown to enhance the metabolism of E coli. Under microaerobic conditions, Vhb raises the intracellular dissolved oxygen concentration and increases the transcriptional activity of various oxygen-regulated promoters. The transcriptional activity of the promoter for cytochrome d is shown to increase 1.5-fold. In addition, Fnr, a global regulator in E. coli, activates the transcriptional activity of the heterologous promoter for Vhb. The use of Vhb may provide a method to investigate the aerobic physiology of E. coli and other microorganisms, and it may be exploited to increase process productivity.
8. Aristidou AA, San K-Y, Bennett GN: Metabolic engineering of Escherichia coli to enhance recombinant protein production through acetate reduction. Biotechnol Prog 1995, 11:475-478. The investigators successfully demonstrate their hypothesis that acetate production can be reduced by drawing carbon away to the production of acetoin, which is less toxic to E. coli. The gene encoding acetolactate synthase from B. subtilis is introduced into E. coli. Cell densities are increased by 35% and recombinant protein production is increased by 60% compared with the wild type.
9. Aristidou AA, San K-Y, Bennett GN: Modification of central metabolic pathway in Escherichia coli to reduce acetate accumulation by heterologous expression of the Bacillus subtilis acetolactate synthase gene. Biotechnol Bioeng 1994, 44:944-951,
10. -1 are achieved in complex media. This investigation provides additional evidence that controlling the glycolytic flux is an effective way to reduce acetate production.
11. Goel A, Lee J, Domach MM, Ataai MM: Suppressed acid formation by co-feeding of glucose and citrate in Bacillus cultures: emergence of pyruvate kinase as a potential metabolic engineering site. Biotechnol Prog 1995, 11:380-385. This investigation provides strong evidence that the unequal fluxes between glycolysis and the TCA cycle cause an increased production of acetate. The reduction of the glycolytic flux by the addition of citrate to the medium is shown to cause a suppression of acetate accumulation. Interestingly, the addition of other TCA intermediates does not cause the same effect. This points to the possibility of an unknown specific mechanism for citrate that decreases acetate accumulation.
12. Zhang M, Franden MA, Newman M, McMillan J, Finkelstein M, Picataggio S: Promising ethanologens for xylose fermentation. Appl Biochem Biotechnol 1995, 51/52:527-536.
13. Zhang M, Eddy C, Deanda K, Finkelstein M, Picataggio S: Metabolic engineering of a pentose metabolism pathway in ethanologenic Zymomonas mobilis. Science 1995, 267:240-243. Z. mobilis is successfully engineered to utilize xylose for ethanol production by introducing a xylose assimilation pathway and two genes encoding transketolase and transaldolase. By constructing a complete pentose phosphate pathway, Z. mobilis is able to ferment xylose and produce ethanol at up to 86% of the theoretical yield. Fermentation of a mixture of xylose and glucose yields ethanol production at 95% of the theoretical yield. This investigation represents a significant advance toward sustainable ethanol production from renewable resources.
14. Lindsay SE, Bothast RJ, Ingram LO: Improved strains of recombinant Escherichia coli for ethanol production from sugar mixtures. Appl Microbiol Biotechnol 1995, 43:70-75.
15. Nair RV, Papoutsakis ET: Expression of plasmid-encoded aad in Clostridium acetobutylicum M5 restores vigorous butanol production. J Bacteriol 1994, 176:5843-5846. Genetic complementation is used to show that the primary function of Aad, the gene product of aad, is to form butanol. In addition, plasmid-encoded aad restores butyraldehyde dehydrogenase activity to a strain deficient in any solventogenic enzyme activity. Butanol accumulates in the medium to levels of 84 mM. Further investigations are required to map out the solventogenic pathways of C. acetobutylicum.
16. Girbal L, Soucaille P: Regulation of Clostridium acetobutylicum metabolism, as revealed by mixed-substrate steady-state continuous cultures: role of NADH/NAD ratio and ATP pool. J Bacteriol 1994, 176:6433-6438. This extensive physiological study on C. acetobutylicum reveals further insight into the function of the ATP pool and the NADH/NAD ratio on product selectivity.
17. Papoutsakis ET: A useful equation for fermentations of butyric acid bacteria. In The Acetone-Butanol Fermentation and Related Topics. Science and Technology Letters. Edited by Bu'Lock JD, Bu'lock AJ. Kew; Chameleon Press Ltd; 1983:121-126.
18. Frost JW, Lievense J: Prospects for the biocatalytic synthesis of aromatics in the 21st century. New J Chem 1994, 18:341-348.
19. Patnaik R, Liao JC: Engineering of Escherichia coli central metabolism for aromatic metabolite production with near theoretical yield. Appl Environ Microbiol 1994, 60:3903-3908. Owing to the action of the PTS, PEP is the limiting factor in the production of aromatic amino acids in E coli. By recycling pyruvate to PEP and directing carbon flux to the production of PEP and E4P, production of aromatic amino acids approaches a maximum yield of 86% (mol/mol) from glucose. This work demonstrates that the PTS is a critical component that needs to be considered in designing metabolic pathways.
20. Palnaik R, Spitzer RG, Liao JC: Pathway engineering for production of aromatics in Escherichia coli: confirmation of stoichiometric analysis by independent modulation of AroG, TktA, and PpS activities. Biotechnol Bioeng 1995, 46:361-370. This investigation examines the roles of AroG, TktA, and PPS in the production of aromatics in E. coli. Independent promoters are used to control the expression levels of these enzymes. Results confirm the prediction from stoichiometric analysis. Furthermore, xylose, a sugar transported into E. coli independently from the PTS, is tested as a substrate for the production of aromatic amino acids. Because the PTS is not involved with xylose assimilation, the yield of aromatic amino acids on xylose should be comparable to the yield on glucose, without having to recycle pyruvate back to PEP. Indeed, this hypothesis is verified and a yield of 71% (mol/mol) on xylose is obtained.
21. Ikeda M, Katsumata R: Transport of aromatic amino acids and its influence on overproduction of the amino acids in Corynebacterium glutamicum. J Ferment Bioeng 1994, 78:420-425.
22. Dudley MW, Frost JW: Biocatalytic desulfurization of arylsulfonates. Bioorg Med Chem 1994, 2:681-690.
23. Sahm H, Eggeling L, Eikmanns B, Kramer R: Metabolic design in amino acid producing bacterium Corynebacterium glutamicum. FEMS Microbiol Rev 1995, 16:243-252.
24. Jetten MSM, Sinskey AJ: Recent advances in the physiology and genetics of amino acid-producing bacteria. Crit Rev Biotechnol 1995, 15:73-103.
25. Gubler M, Jetten M, Lee SH, Sinskey AJ: Cloning of the pyruvate kinase gene (pyk) of Corynebacterium glutamicum and site-specific inactivatlon of pyk in a lysine-producing Corynebacterium lactofermentum strain. Appl Environ Microbiol 1994, 60:2494-2500.
26. -1.
27. Motoyama H, Yano H, Ishina S, Anazawa H: Effects of the amplification of the genes coding for the L-threonine biosynthetic enzymes on the L-threonlne production from methanol by a Gram-negative obligate methylotroph, Methylobacillus glycogenes. Appl Microbiol Biotechnol 1994, 42:67-72.
28. -1 in a shake-flask fermentation is reported.
29. French CE, Hailes AM, Rathbone DA, Long MT, Willey DL, Bruce NC: Biological production of semisynthetic opiates using genetically engineered bacteria. Biotechnology 1995, 13:674-676.
30. Tong IT, Cameron DC: Enhancement of 1,3-propanediol production by cofermentation in Escherichia coli expressing Klebsiella pneumoniae dha regulon genes. Appl Biochem Biotechnol 1992, 34/35:149-159.
31. Tong IT, Liao HH, Cameron DC: 1,3-Propanediol production by Escherichia coli expressing genes from the Klebsiella pneumoniae dha regulon. Appl Environ Microbiol 1991, 57:3541-3546.
32. Jackson DE, Srienc F: Novel methods to synthesize polyhydroxyalkanoates. Ann NY Acad Sci 1994, 745:134-148.
33. -1 PHB within 32 h. K. oxytoca is reported to produce the co-polymer P(3HB-co-3HV) when propionate is added to the medium. This investigation takes advantage of a major strength of polymer production in bacterial hosts by utilizing cheaper alternative carbon sources as substrates.
34. + Escherichia coli. Appl Environ Microbiol 1995, 61:2487-2492.
35. Poirier Y, Nawrath C, Somerville C: Production of polyhydroxyalkanoates, a family of biodegradable plastics and elastomers, in bacteria and plants. Biotechnology 1995, 13:142-150
36. Van der Leij FR, Witholt B: Strategies for the sustainable production of new biodegradable polyesters in plants: a review. Can J Microbiol 1995, 41:222-238.
37. Nawrath C, Poirier Y, Somerville C: Targeting of the polyhydroxybutyrate biosynthetic pathway to the plastids of Arabidopsis thaliana results in high levels of polymer accumulation. Proc Natl Acad Sci USA 1994, 91:12760-12764. PHB is produced in high amounts in A thaliana by targeting the PHB biosynthetic pathway from A eutrophus to the plastids The investigators successfully hypothesize that the localization of PHB production to a compartment with a high acetyl-CoA flux would not adversely affect the growth of the plant. PHB accumulates to levels up to 14% of the dry weight of the plant.
38. Poirier Y, Dennis DE, Klomparens K, Somerville CR: Polyhydroxybutyrate, a biodegradable thermoplastic, produced in transgenlc plants. Science 1992, 256:520-523.
39. Jeffries TW, Kurtzmann CP: Strain selection, taxonomy, and genetics of xylose-fermenting yeasts. Enzyme Microb Technol 1994, 16:922-932
40. Hahn-Hagerdal B, Jeppsson H, Skoog K, Prior BA: Biochemistry and physiology of xylose fermentation by yeasts. Enzyme Microb Technol 1994, 16:933-943.