Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Towards bacterial strains overproducing l-tryptophan and other aromatics by metabolic engineering

Abstract

The aromatic amino acids, l-tryptophan, l-phenylalanine, and l-tyrosine, can be manufactured by bacterial fermentation. Until recently, production efficiency of classical aromatic amino-acid-producing mutants had not yet reached a high level enough to make the fermentation method the most economic. With the introduction of recombinant DNA technology, it has become possible to apply more rational approaches to strain improvement. Many recent activities in this metabolic engineering have led to several effective approaches, which include modification of terminal pathways leading to removal of bottleneck or metabolic conversion, engineering of central carbon metabolism leading to increased supply of precursors, and transport engineering leading to reduced intracellular pool of the aromatic amino acids. In this review, advances in metabolic engineering for the production of the aromatic amino acids and useful aromatic intermediates are described with particular emphasis on two representative producer organisms, Corynebacterium glutamicum and Escherichia coli.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Aiba S, Tsunekawa H, Imanaka T (1982) New approach to tryptophan production by Escherichia coli: genetic manipulation of composite plasmids in vitro. Appl Environ Microbiol 43:289–297

  2. Azuma S, Tsunekawa H, Okabe M, Okamoto R, Aiba S (1993) Hyper-production of l-tryptophan via fermentation with crystallization. Appl Microbiol Biotechnol 39:471–476

  3. Backman K, O’Connor MJ, Maruya A, Rudd E, McKay D, Balakrishnan R, Radjai M, DiPasquantonio V, Shoda D, Hatch R, Venkatasubramanian K (1990) Genetic engineering of metabolic pathways applied to the production of phenylalanine. Ann N Y Acad Sci 589:16–24

  4. Backman KC (1992) Method of biosynthesis of phenylalanine. US Patent 5,169,768

  5. Bell JK, Pease PJ, Bell JE, Grant GA, Banazak LJ (2002) De-regulation of d-3-phosphoglycerate dehydrogenase by domain removal. Eur J Biochem 269:4176–4184

  6. Berry A (1996) Improving production of aromatic compounds in Escherichia coli by metabolic engineering. Trends Biotechnol 14:250–256

  7. Bongaerts J, Krämer M, Müller U, Raeven L, Wubbolts M (2001) Metabolic engineering for microbial production of aromatic amino acids and derived compounds. Metab Eng 3:289–300

  8. Caligiuri MG, Bauerle R (1991) Identification of amino acid residues involved in feedback regulation of the anthranilate synthase complex from Salmonella typhimurium. Evidence for an amino-terminal regulatory site. J Biol Chem 266:8328–8335

  9. Camakaris H, Cowan P, Pittard J (1997) Production of tryptophan by the bacterium Escherichia coli. European Patent Appl 789,073

  10. Chan E-C, Tsai H-L, Chen S-L, Mou D-G (1993) Amplification of the tryptophan operon gene in Escherichia coli chromosome to increase l-tryptophan biosynthesis. Appl Microbiol Biotechnol 40:301–305

  11. Chandran SS, Yi J, Draths KM, Von Daeniken R, Weber W, Frost JW (2003) Phosphoenolpyruvate availability and the biosynthesis of shikimic acid. Biotechnol Prog 19:808–814

  12. del Real G, Aguilar A, Martín JF (1985) Cloning and expression of tryptophan genes from Brevibacterium lactofermentum in Escherichia coli. Biochem Biophys Res Commun 133:1013–1019

  13. Draths KM, Knop DR, Frost JW (1999) Shikimic acid and quinic acid: replacing isolation from plant sources with recombinant microbial biocatalysis. J Am Chem Soc 121:1603–1604

  14. Edwards RM, Taylor PP, Hunter MG, Fotheringham IG (1987) Composite plasmids for amino acid synthesis. WO8,700,202

  15. Eggeling L, Bott M (2005) Handbook of Corynebacterium glutamicum. CRC Press, Boca Raton, FL

  16. Eggeling L, Sahm H (2001) The cell wall barrier of Corynebacterium glutamicum and amino acid efflux. J Biosci Bioeng 92:201–213

  17. Flores N, Xiao J, Berry A, Bolivar F, Valle F (1996) Pathway engineering for the production of aromatic compounds in Escherichia coli. Nat Biotechnol 14:620–623

  18. Frost JW (1992) Enhanced production of common aromatic pathway compounds. US Patent 5,168,056

  19. Frost JW (1994) Prospects for biocatalytic synthesis of aromatics in the 21st century. New J Chem 18:341–348

  20. Gething MJH, Davidson BE, Dopheide TAA (1976) Chorismate mutase/prephenate dehydratase from Escherichia coli K 12. Eur J Biochem 71:317–325

  21. Gerigk MR, Maass D, Kreutzer A, Sprenger G, Bongaerts J, Wubbolts M, Takors R (2002a) Enhanced pilot-scale fed-batch l-phenylalanine production with recombinant Escherichia coli by fully integrated reactive extraction. Bioprocess Biosyst Eng 25:43–52

  22. Gerigk MR, Bujnicki R, Ganpo-Nkwenkwa E, Bongaerts J, Sprenger G, Takors R (2002b) Process control for enhanced l-phenylalanine production using different recombinant Escherichia coli strains. Biotechnol Bioeng 80:746–754

  23. Gosset G, Yong-Xiao J, Berry AA (1996) Direct comparison of approaches for increasing carbon flow to aromatic biosynthesis in Escherichia coli. J Ind Microbiol 17:47–52

  24. Grant GA, Xu XL, Hu Z (2000) Removal of the tryptophan 139 side chain in Escherichia colid-3-phosphoglycerate dehydrogenase produces a dimeric enzyme without cooperative effects. Arch Biochem Biophys 375:171–174

  25. Grant GA, Hu Z, Xu XL (2001) Amino acid residue mutations uncouple cooperative effects in Escherichia colid-3-phosphoglycerate dehydrogenase. J Biol Chem 276:17844–17850

  26. Grant GA, Hu Z, Xu XL (2002) Cofactor binding to Escherichia colid-3-phosphoglycerate dehydrogenase induces multiple conformations which alter effector binding. J Biol Chem 277:39548–39553

  27. Grinter NJ (1998) Developing an l-phenylalanine process. Chemtech 28:33–35

  28. Hagino H, Nakayama K (1975) Regulatory properties of anthranilate synthase from Corynebacterium glutamicum. Agric Biol Chem 39:323–330

  29. Heery DM, Dunican LK (1993) Cloning of the trp gene cluster from a tryptophan-hyperproducing strain of Corynebacterium glutamicum: identification of a mutation in the trp leader sequence. Appl Environ Microbiol 59:791–799

  30. Hermann T (2003) Industrial production of amino acids by coryneform bacteria. J Biotechnol 104:155–172

  31. Herrmann KM (1983) The common aromatic biosynthetic pathway. In: Herrmann KM, Somerville RL (eds) Amino acids: biosynthesis and genetic regulation. Addison-Wesley, Reading, MA, pp 301–322

  32. Hsu SK, Lin LL, Lo HH, Hsu WH (2004) Mutational analysis of feedback inhibition and catalytic sites of prephenate dehydratase from Corynebacterium glutamicum. Arch Microbiol 181:237–244

  33. Ikeda M (2003) Amino acid production processes. In: Faurie R, Thommel J (eds) Microbial production of l-amino acids. Advances in biochemical engineering/biotechnology, vol 79. Springer, Berlin Heidelberg New York, pp 1–35

  34. Ikeda M, Katsumata R (1992) Metabolic engineering to produce tyrosine or phenylalanine in a tryptophan-producing Corynebacterium glutamicum strain. Appl Environ Microbiol 58:781–785

  35. Ikeda M, Katsumata R (1994) Transport of aromatic amino acids and its influence on overproduction of the amino acids in Corynebacterium glutamicum. J Ferment Bioeng 78:420–425

  36. Ikeda M, Katsumata R (1995) Tryptophan production by transport mutants of Corynebacterium glutamicum. Biosci Biotech Biochem 59:1600–1602

  37. Ikeda M, Katsumata R (1999) Hyperproduction of tryptophan by Corynebacterium glutamicum with the modified pentose phosphate pathway. Appl Environ Microbiol 65:2497–2502

  38. Ikeda M, Nakagawa S (2003) The Corynebacterium glutamicum genome: features and impacts on biotechnological processes. Appl Microbiol Biotechnol 62:99–109

  39. Ikeda M, Ozaki A, Katsumtata R (1993) Phenylalanine production by metabolically engineered Corynebacterium glutamicum with the pheA gene of Escherichia coli. Appl Microbiol Biotechnol 39:318–323

  40. Ikeda M, Nakanishi K, Kino K, Katsumata R (1994) Fermentative production of tryptophan by a stable recombinant strain of Corynebacterium glutamicum with a modified serine-biosynthetic pathway. Biosci Biotech Biochem 58:674–678

  41. Ikeda M, Okamoto K, Katsumata R (1999) Cloning of the transketolase gene and the effect of its dosage on aromatic amino acid production in Corynebacterium glutamicum. Appl Microbiol Biotechnol 51:201–206

  42. Ikeda M, Ohnishi J, Mitsuhashi S (2005) Genome breeding of an amino acid-producing Corynebacterium glutamicum Mutant. In: Barredo JLS (ed) Microbial processes and products. Humana Press, Totowa, NJ, pp 179–189

  43. Ito H, Sato K, Enei H, Hirose Y (1990a) Improvement in microbial production of l-tyrosine by gene dosage effect of aroL gene encoding shikimate kinase. Agric Biol Chem 54:823–824

  44. Ito H, Sato K, Matsui K, Sano K, Enei H, Hirose Y (1990b) Molecular breeding of a Brevibacterium lactofermentuml-phenylalanine producer using a cloned prephenate dehydratase gene. Appl Microbiol Biotechnol 33:190–195

  45. Ito H, Sato K, Matsui K, Sano K, Nakamori S, Tanaka T, Enei H (1990c) Cloning and characterization of genes responsible for m-fluoro-d,l-phenylalanine resistance in Brevibacterium lactofermentum. Agric Biol Chem 54:707–713

  46. Kalinowski J, Bathe B, Bartels D, Bischoff N, Bott M, Burkovski A, Dusch N, Eggeling L, Eikmanns B, Gaigalat L, Goesmann A, Hartmann M, Huthmacher K, Krämer R, Linke B, McHardy AC, Meyer F, Möckel B, Pfefferle W, Pühler A, Rey DA, Rückert C, Rupp O, Sahm H, Wendisch VF, Wiegräbe I, Tauch A (2003) The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of l-aspartate-derived amino acids and vitamins. J Biotechnol 104:5–25

  47. Kamada N, Yasuhara A, Takano Y, Nakano T, Ikeda M (2001) Effect of transketolase modifications on carbon flow to the purine-nucleotide pathway in Corynebacterium ammoniagenes. Appl Microbiol Biotechnol 56:710–717

  48. Katsumata R, Kino K (1989) Process for producing amino acids by fermentation. Japan Patent 01,317,395 A (P2,578,488)

  49. Katsumata R, Ikeda M (1993) Hyperproduction of tryptophan in Corynebacterium glutamicum by pathway engineering. Biotechnology 11:921–925

  50. Katsumata R, Ozaki A, Oka T, Furuya A (1984) Protoplast transformation of glutamate-producing bacteria with plasmid DNA. J Bacteriol 159:306–311

  51. Katsumata R, Ikeda M, Nakanishi K, Sasao Y (1997) Process for stably maintaining recombinant plasmids in serine auxotrophic microorganisms belonging to the genus Corynebacterium or Brevibacterium. US Patent 5,595,894

  52. Kikuchi Y, Tsujimoto K, Kurahashi O (1997) Mutational analysis of the feedback sites of phenylalanine-sensitive 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase of Escherichia coli. Appl Environ Microbiol 63:761–762

  53. Kim, CU, Lew W, Williams MA, Liu H, Zhang L, Swaminathan S, Bischhofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (1997) Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 119:681–690

  54. Knop DR, Draths KM, Chandran SS, Barker JL, Frost JW (2001) Hydroaromatic equilibrium during biosynthesis of shikimic acid. J Am Chem Soc 123:10173–10182

  55. Koehn SJ, Evans TM, Nelson RA, Taylor PP (1994) Methods for increasing carbon conversion efficiency in microorganisms. WO9,428,154

  56. Konstantinov KB, Yoshida T (1992) The way to adequate control of microbial processes passes via real-time knowledge-based supervision. J Biotechnol 24:33–51

  57. Konstantinov KB, Nishio N, Seki T, Yoshida T (1991) Physiologically motivated strategies for control of the fed-batch cultivation of recombinant Escherichia coli for phenylalanine production. J Ferment Bioeng 71:350–355

  58. Krämer R (1994) Systems and mechanisms of amino acid uptake and excretion in prokaryotes. Arch Microbiol 162:1–13

  59. Krämer R, Boles E, Eggeling L, Erdmann A, Gutmann M, Kronemeyer W, Palmieri L, Zittrich S (1994) Mechanism and energetics of amino-acid transport in coryneform bacteria. Biochim Biophys Acta 1187:245–249

  60. Krämer M, Bongaerts J, Bovenberg R, Kremer S, Müller U, Orf S, Wubbolts M, Raeven L (2003) Metabolic engineering for microbial production of shikimic acid. Metab Eng 5:277–283

  61. Leuchtenberger W (1996) Amino acids—technical production and use. In: Roehr M (ed) Products of primary metabolism, 2nd edn. Biotechnology, vol 6. VCH, Weinheim, pp 465–502

  62. Li K, Frost JW (1999) Microbial synthesis of 3-dehydroshikimic acid: a comparative analysis of d-xylose, l-arabinose, and d-glucose carbon sources. Biotechnol Prog 15:876–883

  63. Li K, Mikola MR, Draths KM, Worden RM, Frost JW (1999) Fed-batch fermentor synthesis of 3-dehydroshikimic acid using recombinant Escherichia coli. Biotechnol Bioeng 64:61–73

  64. Liao JC (1996) Microorganisms and methods for overproduction of DAHP by cloned pps gene. WO9,608,567

  65. Liao JC, Hou S-Y, Chao Y-P (1996) Pathway analysis, engineering, and physiological considerations for redirecting central metabolism. Biotechnol Bioeng 52:129–140

  66. Liao H-F, Lin L-L, Chien HR, Hsu W-H (2001) Serine 187 is a crucial residue for allosteric regulation of Corynebacterium glutamicum 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase. FEMS Microbiol Lett 194:59–64

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

  68. Maiti TK, Roy A, Mukherjee SK, Chatterjee SP (1995) Microbial production of l-tyrosine: a review. Hindustan Antibiot Bull 37:51–65

  69. Marx A, Hans S, Möckel B, Bathe B, de Graaf AA (2003) Metabolic phenotype of phosphoglucose isomerase mutants of Corynebacterium glutamicum. J Biotechnol 104:185–197

  70. Mascarenhas D, Ashworth DJ, Chen CS (1991) Deletion of pgi alters tryptophan biosynthesis in a genetically engineered strain of Escherichia coli. Appl Environ Microbiol 57:2995–2999

  71. Matsui K, Sano K, Ohtsubo E (1986) Complete nucleotide and deduced amino acid sequences of the Brevibacterium lactofermentum tryptophan operon. Nucleic Acids Res 14:10113–10114

  72. Matsui K, Miwa K, Sano K (1987a) Two single base pair substitutions causing desensitization to tryptophan feedback inhibition of anthranilate synthase and enhanced expression of tryptophan genes of Brevibacterium lactofermentum. J Bacteriol 109:5330–5332

  73. Matsui K, Miwa K, Sano K (1987b) Cloning of tryptophan genes of Brevibacterium lactofermentum, a glutamic acid-producing bacterium. Agric Biol Chem 51:823–828

  74. Matsui K, Sano K, Ohtsubo E (1987c) Sequence analysis of the Brevibacterium lactofermentumtrp operon. Mol Gen Genet 209:299–305

  75. McHardy AC, Tauch A, Rückert C, Pühler A, Kalinowski J (2003) Genome-based analysis of biosynthetic aminotransferase genes of Corynebacterium glutamicum. J Biotechnol 104:229–240

  76. Miller JE, Backman KC, O’Connor MJ, Hatch RT (1987) Production of phenylalanine and organic acids by phosphoenolpyruvate carboxylase-deficient mutants of Escherichia coli. J Ind Microbiol 2:143–149

  77. Miwa K, Matsui K, Terabe M, Ito K, Ishida M, Takagi H, Nakamori S, Sano K (1985) Construction of novel shuttle vector and a cosmid vector for the glutamic acid-producing bacteria Brevibacterium lactofermentum and Corynebacterium glutamicum. Gene 39:281–286

  78. Nelms J, Gonzalez DH, Yoshida T, Fotheringham I (1992) Novel mutations in the pheA gene of Escherichia coli K-12 which result in highly feedback inhibition-resistant variants of chorismate mutase/prephenate dehydratase. Appl Environ Microbiol 58:2592–2598

  79. Nishio Y, Nakamura Y, Kawarabayashi Y, Usuda Y, Kimura E, Sugimoto S, Matsui K, Yamagishi A, Kikuchi H, Ikeo K, Gojobori T (2003) Comparative complete genome sequence analysis of the amino acid replacements responsible for the thermostability of Corynebacterium efficiens. Genome Res 13:1572–1579

  80. O’gara JP, Dunican LK (1994) Direct evidence for a constitutive internal promoter in the tryptophan operon of Corynebacterium glutamicum. Biochem Biophys Res Commun 203:820–827

  81. Ohnishi J, Mitsuhashi S, Hayashi M, Ando S, Yokoi H, Ochiai K, Ikeda M (2002) A novel methodology employing Corynebacterium glutamicum genome information to generate a new l-lysine-producing mutant. Appl Microbiol Biotechnol 58:217–223

  82. Ohnishi J, Hayashi M, Mitsuhashi S, Ikeda M (2003) Efficient 40°C fermentation of l-lysine by a new Corynebacterium glutamicum mutant developed by genome breeding. Appl Microbiol Biotechnol 62:69–75

  83. Ohnishi J, Katahira R, Mitsuhashi S, Kakita S, Ikeda M (2005) A novel gnd mutation leading to increased l-lysine production in Corynebacterium glutamicum. FEMS Microbiol Lett 242:265–274

  84. Ozaki A, Katsumata R, Oka T, Furuya A (1985) Cloning of the genes concerned in phenylalanine biosynthesis in Corynebacterium glutamicum and its application to breeding of a phenylalanine producing strain. Agric Biol Chem 49:2925–2930

  85. Patil KR, Åkesson M, Nielsen J (2004) Use of genome-scale microbial models for metabolic engineering. Curr Opin Biotechnol 15:64–69

  86. Patnaik R, Liao JC (1994) Engineering of Escherichia coli central metabolism for aromatic metabolite production with near theoretical yield. Appl Environ Microbiol 60:3903–3908

  87. Patnaik R, Spitzer RG, Liao JC (1995) Pathway engineering for production of aromatics in Escherichia coli: confirmation of stoichiometric analysis by independent modulation of AroG, TktA, and Pps activities. Biotechnol Bioeng 46:361–370

  88. Peters-Wendisch P, Netzer R, Eggeling L, Sahm H (2002) 3-Phosphoglycerate dehydrogenase from Corynebacterium glutamicum: the C-terminal domain is not essential for activity but is required for inhibition by l-serine. Appl Microbiol Biotechnol 60:437–441

  89. Pittard AJ (1996) Biosynthesis of the aromatic amino acids. In: Neidhardt FC (ed) Escherichia coli and Salmonella. ASM Press, Washington, DC, pp 458–484

  90. Pittard J, Camakaris H, Yang Ji (2005) The TyrR regulon. Mol Microbiol 55:16–26

  91. Pohnert G, Zhang S, Husain A, Wilson DB, Ganem B (1999) Regulation of phenylalanine biosynthesis. Studies on the mechanism of phenylalanine binding and feedback inhibition in the Escherichia coli P-protein. Biochemistry 38:12212–12217

  92. Polen T, Krämer M, Bongaerts J, Wubbolts M, Wendisch VF (2005) The global gene expression response of Escherichia coli to l-phenylalanine. J Biotechnol 115:221–237

  93. Ray JM, Yanofsky C, Bauerle (1988) Mutational analysis of the catalytic and feedback sites of the tryptophan-sensitive 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase of Escherichia coli. J Bacteriol 170:5500–5506

  94. Sano K, Matsui K (1987) Structure and function of the trp operon control regions of Brevibacterium lactofermentum, a glutamic-acid-producing bacterium. Gene 53:191–200

  95. Santamaria R, Gil JA, Mesas JM, Martin JF (1984) Characterization of an endogenous plasmid and development of cloning vectors and a transformation system in Brevibacterium lactofermentum. J Gen Microbiol 130:2237–2246

  96. Sauer U, Eikmanns BJ (2005) The PEP-pyruvate-oxaloacetate node as the switch point for carbon flux distribution in bacteria. FEMS Microbiol Rev 29:765–794

  97. Schmid JW, Mauch K, Reuss M, Gilles ED, Kremling A (2004) Metab Eng 6:364–377

  98. Shiio I, Miyajima R, Nakagawa M (1972) Regulation of aromatic amino acid biosynthesis in Brevibacterium flavum. I. Regulation of anthranilate synthetase. J Biochem 72:1447–1455

  99. Somerville RL (1983) Tryptophan: biosynthesis, regulation, and large-scale production. In: Herrmann KM, Somerville RL (eds) Amino acids: biosynthesis and genetic regulation. Addison-Wesley, Reading, MA, pp 351–378

  100. Sprenger G, Siewe R, Sahm H, Karutz M, Sonke T (1998a) Microbial preparation of substances from aromatic metabolism. WO9,818,937

  101. Sprenger G, Siewe R, Sahm H, Karutz M, Sonke T (1998b) Microbial preparation of substances from aromatic metabolism. WO9,818,936

  102. Suga M, Sugimoto M, Osumi T, Nakamatsu T, Hibino W, Ito M (2000) Method of producing l-serine by fermentation. US Patent 6,037,154

  103. Sugimoto S, Shiio I (1974) Regulation of prephenate dehydratase in Brevibacterium flavum. J Biochem 76:1103–1111

  104. Sugimoto S, Shiio I (1977) Enzymes of the tryptophan synthetic pathway in Brevibacterium flavum. J Biochem 81:823–833

  105. Sugimoto S, Shiio I (1980a) Purification and properties of bifunctional 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase-chorismate mutase component A from Brevibacterium flavum. J Biochem 87:881–890

  106. Sugimoto S, Shiio I (1980b) Purification and properties of dissociable chorismate mutase from Brevibacterium flavum. J Biochem 88:167–176

  107. Sugimoto S, Shiio I (1982) Tryptophan synthase and production of l-tryptophan in regulatory mutants. Agric Biol Chem 46:2711–2718

  108. Sugimoto S, Shiio I (1983) Regulation of tryptophan biosynthesis by feedback inhibition of the second-step enzyme, anthranilate phosphoribosyltransferase, in Brevibacterium flavum. Agric Biol Chem 47:2295–2305

  109. Sugimoto S, Yabuta M, Kato N, Tatsuji S, Yoshida T, Taguchi H (1987) Hyperproduction of phenylalanine by Escherichia coli: application of a temperature-controllable expression vector carrying the repressor–promoter system of bacteriophage lambda. J Biotechnol 5:237–253

  110. Takagi M, Nishio Y, Oh G, Yoshida T (1996) Control of l-phenylalanine production by dual feeding of glucose and l-tyrosine. Biotechnol Bioeng 52:653–660

  111. Tatarko M, Romeo T (2001) Disruption of a global regulatory gene to enhance central carbon flux into phenylalanine biosynthesis in Escherichia coli. Curr Microbiol 43:26–32

  112. Tonouchi N, Kojima H, Matsui H (1997) Recombinant DNA sequences encoding feedback inhibition released enzymes, plasmids comprising the recombinant DNA sequences, transformed microorganisms useful in the production of aromatic amino acids, and a process for preparing aromatic amino acids by fermentation. EP 0,488,424 B1

  113. Tribe DE, Pittard J (1979) Hyperproduction of tryptophan by Escherichia coli: genetic manipulation of the pathways leading to tryptophan formation. Appl Environ Microbiol 38:181–190

  114. Umbarger HE (1978) Amino acid biosynthesis and its regulation. Annu Rev Biochem 47:533–606

  115. Weaver LM, Herrmann KM (1990) Cloning of an aroF allele encoding a tyrosine-insensitive 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase. J Bacteriol 172:6581–6584

  116. Wehrmann A, Morakkabati S, Krämer R, Sahm H, Eggeling L (1995) Functional analysis of sequences adjacent to dapE of Corynebacterium glutamicum reveals the presence of aroP, which encodes the aromatic amino acid transporter. J Bacteriol 177:5991–5993

  117. Yajima Y, Sakimoto K, Takahashi K, Miyao K, Kudome Y, Aichi K (1990) l-Tryptophan-producing microorganism and production of l-tryptophan. Japan Patent Appl 02,190,182

  118. Yoshihama M, Higashiro K, Rao EA, Akedo M, Shanabruch WG, Folletie MT, Walker GC, Sinskey AJ (1985) Cloning vector system for Corynebacterium glutamicum. J Bacteriol 162:591–597

  119. Yurievich GA, Vladimirovna BI, Vadimovich ZD, Yuriev SA, Dmitrievich KA, Valentinovna BA, Vladimirovich MS (2004) Method for producing l-amino acid using bacterium having enhanced expression of pckA gene. WO2,004,090,125

  120. Zhang S, Pohnert G, Kongsaeree P, Wilson DB, Clardy J, Ganem B (1998) Chorismate mutase/prephenate dehydratase from Escherichia coli. Study of catalytic and regulatory domains using genetically engineered proteins. J Biol Chem 273:6248–6253

Download references

Author information

Correspondence to Masato Ikeda.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ikeda, M. Towards bacterial strains overproducing l-tryptophan and other aromatics by metabolic engineering. Appl Microbiol Biotechnol 69, 615–626 (2006). https://doi.org/10.1007/s00253-005-0252-y

Download citation

Keywords

  • Metabolic Engineering
  • Aromatic Amino Acid
  • Anthranilic Acid
  • Central Metabolism
  • Aromatic Amino Acid Biosynthesis