Metabolic engineering of glutamate production.

Since the discovery of Corynebacterium glutamicum as an efficient glutamate-overproducing microorganism in 1957, the production of L-amino acids by the fermentative method has become one of the most important research-target of industrial microbiology. Several research groups have developed metabolic engineering principles for L-amino acid-producing C. glutamicum strains over the last four decades. The mechanism of L-glutamate-overproduction by the microorganism is very unique and interesting. L-Glutamate overproduction by this bacterium, a biotin auxotroph, is induced by a biotin limitation and suppressed by an excess of biotin. Addition of a surfactant or penicillin is known to induce L-glutamate overproduction under excess biotin. After the development of the general molecular biology tools such as cloning vectors and DNA transfer technique, genes encoding biosynthetic enzymes were isolated. With those genes and tools, recombinant DNA technology can be applied in analysis of biosynthetic pathways and strain construction of C. glutamicum. In this review, key points of the L-glutamate biosynthetic pathways are summarized and the recent studies about triggering mechanism of L-glutamate overproduction by C. glutamicum are introduced. Then the metabolic flux analysis of L-glutamate overproduction is explored.

[1]  Kazuhiko Yamada,et al.  TAXONOMIC STUDIES ON CORYNEFORM BACTERIA:IV. MORPHOLOGICAL, CULTURAL, BIOCHEMICAL, AND PHYSIOLOGICAL CHARACTERISTICS , 1972 .

[2]  A. D. de Graaf,et al.  Response of the central metabolism of Corynebacterium glutamicum to different flux burdens. , 1997, Biotechnology and bioengineering.

[3]  S. Schiffman Sensory enhancement of foods for the elderly with monosodium glutamate and flavors , 1998 .

[4]  A. Bunch,et al.  The manipulation of micro-organisms for the production of secondary metabolites. , 1986, Biotechnology & genetic engineering reviews.

[5]  H. Ertan The effect of various culture conditions on the levels of ammonia assimilatory enzymes of Corynebacterium callunae , 2004, Archives of Microbiology.

[6]  M. Ikeda,et al.  Hyperproduction of L-threonine by an Escherichia coli mutant with impaired L-threonine uptake. , 1997, Bioscience, biotechnology, and biochemistry.

[7]  G. Stephanopoulos,et al.  Elucidation of anaplerotic pathways in Corynebacterium glutamicum via 13C-NMR spectroscopy and GC-MS , 1997, Applied Microbiology and Biotechnology.

[8]  H. Sung,et al.  Ammonia Assimilation by Glutamine Synthetase/Glutamate Syhthase System in Brevibacterium flavum , 1985 .

[9]  M. Cocaign-Bousquet,et al.  Carbon-flux distribution in the central metabolic pathways of Corynebacterium glutamicum during growth on fructose. , 1998, European journal of biochemistry.

[10]  H. Willard,et al.  Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[11]  H. Wood,et al.  Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli , 1993, Journal of bacteriology.

[12]  H Sahm,et al.  the Czech Republic, , 2022 .

[13]  Volker F. Wendisch,et al.  Pyruvate carboxylase as an anaplerotic enzyme in Corynebacterium glutamicum. , 1997, Microbiology.

[14]  M. Darlison,et al.  Nucleotide sequence of the sucA gene encoding the 2-oxoglutarate dehydrogenase of Escherichia coli K12. , 1984, European journal of biochemistry.

[15]  K. Schleifer,et al.  Transfer of Brevibacterium divaricatum DSM 20297T, “Brevibacterium flavum” DSM 20411, “Brevibacterium lactofermentum” DSM 20412 and DSM 1412, and Corynebacterium lilium DSM 20137T to Corynebacterium glutamicum and Their Distinction by rRNA Gene Restriction Patterns , 1991 .

[16]  A. D. de Graaf,et al.  In Vivo Fluxes in the Ammonium-Assimilatory Pathways in Corynebacterium glutamicum Studied by15N Nuclear Magnetic Resonance , 1999, Applied and Environmental Microbiology.

[17]  K. Matsushita,et al.  NADPH Oxidase System as a Superoxide-generating Cyanide-Resistant Pathway in the Respiratory Chain of Corynebacterium glutamicum. , 1998, Bioscience, biotechnology, and biochemistry.

[18]  E. Kimura,et al.  A dtsR gene-disrupted mutant of Brevibacterium lactofermentum requires fatty acids for growth and efficiently produces L-glutamate in the presence of an excess of biotin. , 1997, Biochemical and biophysical research communications.

[19]  B. Magasanik Genetic control of nitrogen assimilation in bacteria. , 1982, Annual review of genetics.

[20]  A. Demain,et al.  Product inhibition of the fermentative formation of glutamic acid. , 1970, Applied microbiology.

[21]  I. Shiio,et al.  Significance of α-Ketoglutaric Dehydrogenase on the Glutamic Acid Formation in Brevibacterium flavum , 1961 .

[22]  H. Sahm,et al.  Characterization of the isocitrate lyase gene from Corynebacterium glutamicum and biochemical analysis of the enzyme , 1994, Journal of bacteriology.

[23]  J. May,et al.  THE EFFECT OF GROWTH AT ELEVATED TEMPERATURES ON SOME HERITABLE PROPERTIES OF STAPHYLOCOCCUS AUREUS. , 1964, Journal of general microbiology.

[24]  C. Hoischen,et al.  Membrane alteration is necessary but not sufficient for effective glutamate secretion in Corynebacterium glutamicum , 1990, Journal of bacteriology.

[25]  J. Kalinowski,et al.  A Corynebacterium glutamicum gene encoding a two-domain protein similar to biotin carboxylases and biotin-carboxyl-carrier proteins , 1996, Archives of Microbiology.

[26]  G. Stephanopoulos,et al.  Effects of phosphoenol pyruvate carboxylase deficiency on metabolism and lysine production in Corynebacterium glutamicum , 1994, Applied Microbiology and Biotechnology.

[27]  T. Kanzaki,et al.  L-Glutamic Acid Fermentation , 1967 .

[28]  C. Hoischen,et al.  Carrier-mediated glutamate secretion by Corynebacterium glutamicum under biotin limitation. , 1992, Biochimica et biophysica acta.

[29]  H Sahm,et al.  Cloning, sequence analysis, expression, and inactivation of the Corynebacterium glutamicum icd gene encoding isocitrate dehydrogenase and biochemical characterization of the enzyme , 1995, Journal of bacteriology.

[30]  S. Udaka SCREENING METHOD FOR MICROORGANISMS ACCUMULATING METABOLITES AND ITS USE IN THE ISOLATION OF MICROCOCCUS GLUTAMICUS , 1960, Journal of bacteriology.

[31]  B. Eikmanns Identification, sequence analysis, and expression of a Corynebacterium glutamicum gene cluster encoding the three glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase, and triosephosphate isomerase , 1992, Journal of bacteriology.

[32]  H. Sahm,et al.  Glutamate Dehydrogenase Is Not Essential for Glutamate Formation by Corynebacterium glutamicum , 1993, Applied and environmental microbiology.

[33]  M. Follettie,et al.  The phosphoenolpyruvate carboxylase gene of Corynebacterium glutamicum: Molecular cloning, nucleotide sequence, and expression , 1989, Molecular and General Genetics MGG.

[34]  S. Ishino,et al.  13C nuclear magnetic resonance studies of glucose metabolism in L-glutamic acid and L-lysine fermentation by Corynebacterium glutamicum. , 1991 .

[35]  A. Demain,et al.  Biology of industrial microorganisms , 1985 .

[36]  A J Sinskey,et al.  Metabolic and physiological studies of Corynebacterium glutamicum mutants. , 1997, Biotechnology and bioengineering.

[37]  A. Sinskey,et al.  Recent advances in the physiology and genetics of amino acid-producing bacteria. , 1995, Critical reviews in biotechnology.

[38]  J. Kalinowski,et al.  A physical and genetic map of theCorynebacterium glutamicum ATCC 13032 chromosome , 1996, Molecular and General Genetics MGG.

[39]  H. Sahm,et al.  Nucleotide sequence, expression and transcriptional analysis of the Corynebacterium glutamicum gltA gene encoding citrate synthase. , 1994, Microbiology.

[40]  H. Ertan Some properties of glutamate dehydrogenase, glutamine synthetase and glutamate synthase from Corynebacterium callunae , 2004, Archives of Microbiology.

[41]  D. Jézéquel,et al.  Excretion of glutamate from Corynebacterium glutamicum triggered by amine surfactants. , 1992, Biochimica et biophysica acta.

[42]  H. Sung,et al.  Production and Preparation of Glutamate Synthase from Brevibacterium flavum , 1984 .

[43]  P. Carlsson,et al.  Genetic characterization of Bacillus subtilis odhA and odhB, encoding 2-oxoglutarate dehydrogenase and dihydrolipoamide transsuccinylase, respectively , 1989, Journal of bacteriology.

[44]  C. Hoischen,et al.  Evidence for an efflux carrier system involved in the secretion of glutamate by Corynebacterium glutamicum , 1989, Archives of Microbiology.

[45]  M. Takahashi,et al.  Effect of biotin on the bacterial formation of glutamic acid. I. Glutamate formation and cellular premeability of amino acids. , 1962, Journal of biochemistry.

[46]  G. Stephanopoulos,et al.  Metabolic flux distributions in Corynebacterium glutamicum during growth and lysine overproduction , 2000, Biotechnology and bioengineering.

[47]  N. Lindley,et al.  Metabolic analysis of glutamate production by Corynebacterium glutamicum. , 1999, Metabolic engineering.

[48]  A. D. de Graaf,et al.  Ammonia assimilation in Corynebacterium glutamicum and a glutamate dehydrogenase-deficient mutant , 1998, Biotechnology Letters.

[49]  M. Cocaign-Bousquet,et al.  Growth Rate-Dependent Modulation of Carbon Flux through Central Metabolism and the Kinetic Consequences for Glucose-Limited Chemostat Cultures of Corynebacterium glutamicum , 1996, Applied and environmental microbiology.

[50]  A. Demain,et al.  Alteration of permeability for the release of metabolites from the microbial cell. , 1968, Current topics in microbiology and immunology.

[51]  H. Sahm,et al.  Isolation of the Corynebacterium glutamicum glnA gene encoding glutamine synthetase I. , 1997, FEMS microbiology letters.

[52]  P. Bennett,et al.  Reversible inactivation of the isocitrate dehydrogenase of Escherichia coli ML308 during growth on acetate. , 1975, Journal of general microbiology.

[53]  E. Kimura,et al.  Molecular cloning of the Corynebacterium glutamicum ('Brevibacterium lactofermentum' AJ12036) odhA gene encoding a novel type of 2-oxoglutarate dehydrogenase. , 1996, Microbiology.

[54]  S. Udaka,et al.  STUDIES ON THE AMINO ACID FERMENTATION , 1957 .

[55]  S. Nakamori,et al.  Relationship between the glutamate production and the activity of 2-oxoglutarate dehydrogenase in Brevibacterium lactofermentum. , 1997, Bioscience, biotechnology, and biochemistry.

[56]  D. Uy,et al.  Importance of phosphoenolpyruvate carboxylase of Corynebacterium glutamicum during the temperature triggered glutamic acid fermentation. , 1999, Metabolic engineering.

[57]  K. Williams,et al.  Coding sequence of the precursor of the beta subunit of rat propionyl-CoA carboxylase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[58]  H. Sahm,et al.  Structure of the gluABCD cluster encoding the glutamate uptake system of Corynebacterium glutamicum , 1995, Journal of bacteriology.

[59]  Reinhard Krämer,et al.  Secretion of amino acids by bacteria: Physiology and mechanism , 1994 .

[60]  H. Sahm,et al.  Molecular analysis of the Corynebacterium glutamicum gdh gene encoding glutamate dehydrogenase , 1992, Molecular microbiology.

[61]  W. Wiechert,et al.  13C NMR studies of the fluxes in the central metabolism of Corynebacterium glutamicum during growth and overproduction of amino acids in batch cultures , 1995, Applied Microbiology and Biotechnology.

[62]  E. Kimura,et al.  Molecular cloning of a novel gene, dtsR, which rescues the detergent sensitivity of a mutant derived from Brevibacterium lactofermentum. , 1996, Bioscience, biotechnology, and biochemistry.

[63]  D. Banerjee,et al.  Transcriptional regulatory sequences within the first intron of the chicken apolipoproteinAI (apoAI) gene. , 1999, Gene.

[64]  A. Hermetter,et al.  Membrane fluidity in glutamic acid-producing bacteria Brevibacterium sp. ATCC 13869 , 1993, Archives of Microbiology.

[65]  E. Kimura,et al.  Glutamate Overproduction in Corynebacterium glutamicum Triggered by a Decrease in the Level of a Complex Comprising DtsR and a Biotin-containing Subunit. , 1999, Bioscience, biotechnology, and biochemistry.

[66]  I. Shiio,et al.  Purification and some properties of phosphoenolpyruvate carboxylase from Brevibacterium flavum and its aspartate-overproducing mutant. , 1985, Journal of biochemistry.

[67]  Bernhard J. Eikmanns,et al.  Phosphoenolpyruvate carboxylase in Corynebacterium glutamicum is dispensable for growth and lysine production , 1993 .

[68]  Phosphotransferase‐dependent glucose transport in Corynebacterium glutamicum , 1991 .

[69]  I. Shiio,et al.  Enzymes of the glutamate and aspartate synthetic pathways in a glutamate-producing bacterium, Brevibacterium flavum. , 1978, Journal of biochemistry.