Growth Rate-Dependent Modulation of Carbon Flux through Central Metabolism and the Kinetic Consequences for Glucose-Limited Chemostat Cultures of Corynebacterium glutamicum

Cocaign‐Bousquet, Muriel; Guyonvarch, Armel; Lindley, Nic D.

doi:10.1128/aem.62.2.429-436.1996

Cited by 90 publications

(40 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Malic enzyme activity has been detected in C. glutamicum under various growth conditions [237,238,257]. In contrast to the situation in E. coli or B. subtilis, there is only one malic enzyme present in C. glutamicum [117].…”

Section: C4-decarboxylation Reactions In C Glutamicummentioning

confidence: 95%

The PEP—pyruvate—oxaloacetate node as the switch point for carbon flux distribution in bacteria: We dedicate this paper to Rudolf K. Thauer, Director of the Max-Planck-Institute for Terrestrial Microbiology in Marburg, Germany, on the occasion of his 65th birthday

2005

View full text Add to dashboard Cite

In many organisms, metabolite interconversion at the phosphoenolpyruvate (PEP)-pyruvate-oxaloacetate node involves a structurally entangled set of reactions that interconnects the major pathways of carbon metabolism and thus, is responsible for the distribution of the carbon flux among catabolism, anabolism and energy supply of the cell. While sugar catabolism proceeds mainly via oxidative or non-oxidative decarboxylation of pyruvate to acetyl-CoA, anaplerosis and the initial steps of gluconeogenesis are accomplished by C3- (PEP- and/or pyruvate-) carboxylation and C4- (oxaloacetate- and/or malate-) decarboxylation, respectively. In contrast to the relatively uniform central metabolic pathways in bacteria, the set of enzymes at the PEP-pyruvate-oxaloacetate node represents a surprising diversity of reactions. Variable combinations are used in different bacteria and the question of the significance of all these reactions for growth and for biotechnological fermentation processes arises. This review summarizes what is known about the enzymes and the metabolic fluxes at the PEP-pyruvate-oxaloacetate node in bacteria, with a particular focus on the C3-carboxylation and C4-decarboxylation reactions in Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum. We discuss the activities of the enzymes, their regulation and their specific contribution to growth under a given condition or to biotechnological metabolite production. The present knowledge unequivocally reveals the PEP-pyruvate-oxaloacetate nodes of bacteria to be a fascinating target of metabolic engineering in order to achieve optimized metabolite production.

show abstract

Section: C4-decarboxylation Reactions In C Glutamicummentioning

confidence: 95%

The PEP—pyruvate—oxaloacetate node as the switch point for carbon flux distribution in bacteria: We dedicate this paper to Rudolf K. Thauer, Director of the Max-Planck-Institute for Terrestrial Microbiology in Marburg, Germany, on the occasion of his 65th birthday

2005

View full text Add to dashboard Cite

show abstract

“…This con¢rms that glucose is mainly transported by the PTS in C. glutamicum. However, according to Cocagn-Bousquet et al, an additional glucose uptake system besides the glucose PTS could represent up to 15% of the global glucose transport in C. glutamicum at high growth rates [2]. If such a secondary glucose uptake system is present in C. glutamicum, Glk might play an important role in improving rate-limiting reactions and channeling the additional carbon £ux into the pentose phosphate pathway with an ensuing gain in anabolic reducing power.…”

Section: Discussionmentioning

confidence: 99%

“…So, further improvements will most likely involve metabolic engineering of sugar transport capacity and the central pathways. Little relevant information speci¢c to C. glutamicum is available in relation to this [2]. Though glucose metabolism in C. glutamicum is well understood, very little data is available on glucose transport systems and glucose kinase (Glk) at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

“…Because C. glutamicum Glk seems to play a nonessential role in glucose utilization, research interest on this enzyme has been low. However, recently, reports stated that the PTS might not be the only way in which C. glutamicum is able to take up glucose [1,2], suggesting that Glk might play a metabolic role in such an additional glucose transport system. Interestingly, an intrinsic regulatory function of Glk has been reported in Streptomyces coelicolor [5], Bacillus megaterium [6] and Bacillus subtilis [7] in addition to its metabolic function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of glk, a gene coding for glucose kinase of Corynebacterium glutamicum

Park

2000

FEMS Microbiology Letters

View full text Add to dashboard Cite

The glk gene from Corynebacterium glutamicum was isolated by complementation using Escherichia coli ZSC113 (ptsG ptsM glk). We sequenced a total of 3072 bp containing the 969-bp open reading frame encoding glucose kinase (Glk). The glk gene has a deduced molecular mass of 34.2 kDa and contains a typical ATP binding site. Comparison with protein sequences revealed homologies to Glk from Streptomyces coelicolor (43%) and Bacillus megaterium (35%). The glk gene in C. glutamicum was inactivated on the chromosome via single crossover homologous recombination and the resulting glk mutant was characterized. Interestingly, the C. glutamicum glk mutant showed poor growth on rich medium such as LB medium or brain heart infusion medium in the presence or absence of glucose, fructose, maltose or sucrose as the sole carbon source. Growth yield was reduced significantly when maltose was used as the sole carbon source using minimal medium. The growth defect of glk mutant on rich medium was complemented by a plasmid-encoded glk gene. A chromosomal glk^lacZ fusion was constructed and used to monitor glk expression, and it was found that glk was expressed constitutively under all tested conditions with different carbon sources. ß

show abstract

“…This indicates that glucose can be taken up by a different mechanism than the PEP:PTS system in this organism. The PEP:PTS system is absent in Streptomyces species (Hodgson, 1982;Ikeda et al, 1984;Novotna and Hostalek, 1985;Sabater et al, 1972) but exists in parallel with an ATP-dependent glucokinase in the actinomycete C. glutamicum (Cocaign-Bousquet et al, 1996).…”

Section: Identification Of the Metabolic Networkmentioning

confidence: 99%

Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp. ATCC 39727

Gunnarsson

Bruheim

Nielsen

2004

Biotech & Bioengineering

View full text Add to dashboard Cite

The actinomycete Nonomuraea sp. ATCC 39727, producer of the glycopeptide A40926 that is used as precursor for the novel antibiotic dalbavancin, has an unusual carbon metabolism. Glucose is primarily metabolized via the Entner-Doudoroff (ED) pathway, although the energetically more favorable Embden-Meyerhof-Parnas (EMP) pathway is present in this organism. Moreover, Nonomuraea utilizes a PPi-dependent phosphofructokinase, an enzyme that has been connected with anaerobic metabolism in eukaryotes and higher plants, but recently has been recognized in several actinomycetes. In order to study its primary carbon metabolism in further detail, Nonomuraea was cultivated with [1-13C] glucose as the only carbon source and the 13C-labeling patterns of proteinogenic amino acids were determined by GC-MS analysis. Through this method, the fluxes in the central carbon metabolism during balanced growth were estimated. Moreover, a shift in the label incorporation pattern was observed in connection with phosphate limitation and increased antibiotic productivity in Nonomuraea. The shift indicated an increased flux through the EMP pathway at the expense of the flux through the ED pathway, a suggestion that was supported by alterations in intracellular metabolite levels during phosphate limitation. In contrast, expression levels of genes encoding enzymes in the ED and EMP pathways were not affected by phosphate limitation.

show abstract

Growth Rate-Dependent Modulation of Carbon Flux through Central Metabolism and the Kinetic Consequences for Glucose-Limited Chemostat Cultures of Corynebacterium glutamicum

Cited by 90 publications

References 36 publications

The PEP—pyruvate—oxaloacetate node as the switch point for carbon flux distribution in bacteria: We dedicate this paper to Rudolf K. Thauer, Director of the Max-Planck-Institute for Terrestrial Microbiology in Marburg, Germany, on the occasion of his 65th birthday

The PEP—pyruvate—oxaloacetate node as the switch point for carbon flux distribution in bacteria: We dedicate this paper to Rudolf K. Thauer, Director of the Max-Planck-Institute for Terrestrial Microbiology in Marburg, Germany, on the occasion of his 65th birthday

Characterization of glk, a gene coding for glucose kinase of Corynebacterium glutamicum

Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp. ATCC 39727

Contact Info

Product

Resources

About