Project description:Kim2007 - Genome-scale metabolic network of
Mannheimia succiniciproducens (iTY425)
This model is described in the article:
Genome-scale analysis of
Mannheimia succiniciproducens metabolism.
Kim TY, Kim HU, Park JM, Song H, Kim
JS, Lee SY.
Biotechnol. Bioeng. 2007 Jul; 97(4):
657-671
Abstract:
Mannheimia succiniciproducens MBEL55E isolated from bovine
rumen is a capnophilic gram-negative bacterium that efficiently
produces succinic acid, an industrially important four carbon
dicarboxylic acid. In order to design a metabolically
engineered strain which is capable of producing succinic acid
with high yield and productivity, it is essential to optimize
the whole metabolism at the systems level. Consequently, in
silico modeling and simulation of the genome-scale metabolic
network was employed for genome-scale analysis and efficient
design of metabolic engineering experiments. The genome-scale
metabolic network of M. succiniciproducens consisting of 686
reactions and 519 metabolites was constructed based on
reannotation and validation experiments. With the reconstructed
model, the network structure and key metabolic characteristics
allowing highly efficient production of succinic acid were
deciphered; these include strong PEP carboxylation, branched
TCA cycle, relative weak pyruvate formation, the lack of
glyoxylate shunt, and non-PTS for glucose uptake.
Constraints-based flux analyses were then carried out under
various environmental and genetic conditions to validate the
genome-scale metabolic model and to decipher the altered
metabolic characteristics. Predictions based on
constraints-based flux analysis were mostly in excellent
agreement with the experimental data. In silico knockout
studies allowed prediction of new metabolic engineering
strategies for the enhanced production of succinic acid. This
genome-scale in silico model can serve as a platform for the
systematic prediction of physiological responses of M.
succiniciproducens to various environmental and genetic
perturbations and consequently for designing rational
strategies for strain improvement.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180062.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
Project description:Hong2004 - Genome-scale metabolic network of
Mannheimia succiniciproducens (iSH335)
This model is described in the article:
The genome sequence of the
capnophilic rumen bacterium Mannheimia succiniciproducens.
Hong SH, Kim JS, Lee SY, In YH, Choi
SS, Rih JK, Kim CH, Jeong H, Hur CG, Kim JJ.
Nat. Biotechnol. 2004 Oct; 22(10):
1275-1281
Abstract:
The rumen represents the first section of a ruminant
animal's stomach, where feed is collected and mixed with
microorganisms for initial digestion. The major gas produced in
the rumen is CO(2) (65.5 mol%), yet the metabolic
characteristics of capnophilic (CO(2)-loving) microorganisms
are not well understood. Here we report the 2,314,078 base pair
genome sequence of Mannheimia succiniciproducens MBEL55E, a
recently isolated capnophilic Gram-negative bacterium from
bovine rumen, and analyze its genome contents and metabolic
characteristics. The metabolism of M. succiniciproducens was
found to be well adapted to the oxygen-free rumen by using
fumarate as a major electron acceptor. Genome-scale metabolic
flux analysis indicated that CO(2) is important for the
carboxylation of phosphoenolpyruvate to oxaloacetate, which is
converted to succinic acid by the reductive tricarboxylic acid
cycle and menaquinone systems. This characteristic metabolism
allows highly efficient production of succinic acid, an
important four-carbon industrial chemical.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180025.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
Project description:The succinic acid producer Mannheimia succiniciproducens can efficiently utilize sucrose as a carbon source, but its metabolism has not been understood. This study revealed that M. succiniciproducens uses a sucrose phosphotransferase system (PTS), sucrose 6-phosphate hydrolase, and a fructose PTS for the transport and utilization of sucrose.
Project description:Mannheimia succiniciproducens, a rumen bacterium belonging to the family Pasteurellaceae, has two putative ?-galactosidase genes, bgaA and bgaB, encoding polypeptides whose deduced amino acid sequences share 56% identity with each other and show approximately 30% identity to the Escherichia coli gene for LacZ. The M. succiniciproducens bgaA (MsbgaA) gene-deletion mutant was not able to grow on lactose as the sole carbon source, suggesting its essential role in lactose metabolism, whereas the MsbgaB gene-deletion mutant did not show any growth defect on a lactose medium. Furthermore, the expression of the MsbgaA gene was induced by the addition of lactose in the growth medium, whereas the MsbgaB gene was constitutively expressed independently of a carbon source. Biochemical characterization of the recombinant proteins revealed that MsBgaA is more efficient than MsBgaB in hydrolyzing o-nitrophenyl-?-d-galactopyranoside and p-nitrophenyl-?-d-galactopyranoside. MsBgaA was highly specific for the hydrolysis of lactose, with a catalytic efficiency of 46.9 s(-1) mM(-1). However, MsBgaB was more efficient for the hydrolysis of lactulose than lactose, and the catalytic efficiency was 10.0 s(-1) mM(-1). Taken together, our results suggest that the ?-galactosidase paralogues of M. succiniciproducens BgaA and BgaB play a critical role in lactose metabolism and in an unknown but likely specific function for rumen bacteria, respectively.
Project description:Succinic acid is a four-carbon dicarboxylic acid produced as one of the fermentation products of anaerobic metabolism. Based on the complete genome sequence of a capnophilic succinic acid-producing rumen bacterium, Mannheimia succiniciproducens, gene knockout studies were carried out to understand its anaerobic fermentative metabolism and consequently to develop a metabolically engineered strain capable of producing succinic acid without by-product formation. Among three different CO2-fixing metabolic reactions catalyzed by phosphoenolpyruvate (PEP) carboxykinase, PEP carboxylase, and malic enzyme, PEP carboxykinase was the most important for the anaerobic growth of M. succiniciproducens and succinic acid production. Oxaloacetate formed by carboxylation of PEP was found to be converted to succinic acid by three sequential reactions catalyzed by malate dehydrogenase, fumarase, and fumarate reductase. Major metabolic pathways leading to by-product formation were successfully removed by disrupting the ldhA, pflB, pta, and ackA genes. This metabolically engineered LPK7 strain was able to produce 13.4 g/liter of succinic acid from 20 g/liter glucose with little or no formation of acetic, formic, and lactic acids, resulting in a succinic acid yield of 0.97 mol succinic acid per mol glucose. Fed-batch culture of M. succiniciproducens LPK7 with intermittent glucose feeding allowed the production of 52.4 g/liter of succinic acid, with a succinic acid yield of 1.16 mol succinic acid per mol glucose and a succinic acid productivity of 1.8 g/liter/h, which should be useful for industrial production of succinic acid.
Project description:Saccharomyces cerevisiae is an excellent microorganism for industrial succinic acid production, but high succinic acid concentration will inhibit the growth of Saccharomyces cerevisiae then reduce the production of succinic acid. Through analysis the transcriptomic data of Saccharomyces cerevisiae with different genetic backgrounds under different succinic acid stress, we hope to find the response mechanism of Saccharomyces cerevisiae to succinic acid.