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Willy Malaisse – One of the best experts on this subject based on the ideXlab platform.

  • INSULINOTROPIC ACTION OF NOVEL Succinic Acid ESTERS
    Pharmacological research, 1996
    Co-Authors: Fredrik Björkling, F. Malaisse-lagae, Willy Malaisse
    Abstract:

    The insulinotropic action of several new esters of Succinic Acid was assessed in isolated rat islets incubated in the presence of 7 mM D-glucose. An efficient secretory response was observed with the monobenzyl, monoisopropyl, monoallyl, monopropyl, monoethyl, monobutyl, dibutyl, dipropyl and diallyl esters of Succinic Acid. This indicates that it is possible to design esters of Succinic Acid which act as insulin secretagogues, while avoiding the undesirable generation of methanol that otherwise results from the use of either the monomethyl or dimethyl ester of this dicarboxylic Acid.

  • Metabolism of Succinic Acid Methyl Esters in Neural Cells
    Biochemical and molecular medicine, 1995
    Co-Authors: Tie-mei Zhang, Joanne Rasschaert, Willy Malaisse
    Abstract:

    Abstract The metabolism and metabolic effects of Succinic Acid methyl esters were examined in both NG108-15 mouse neuroblastoma × rat glioma hybrid cells and normal rat brain cells. The conversion of the dimethyl ester of 14C-labeled Succinic Acid (10 mM) to 14CO2 only represented 5% or less of that found at an equimolar concentration of D-[U-14C]glucose. Neither the monomethyl nor the dimethyl ester of Succinic Acid exerted any significant effect upon the metabolism of D-glucose. Likewise, D-glucose (10 mM) failed to significantly affect the oxidation of the dimethyl ester of either [1,4-14C]Succinic Acid or [2,3-14C]Succinic Acid. It is concluded that, at variance with the situation recently documented in rat pancreatic islets and hepatocytes, the methyl esters of Succinic Acid are poorly metabolized in neural cells.

  • In vivo stimulation of insulin release by Succinic Acid methyl esters
    Archives internationales de pharmacodynamie et de therapie, 1994
    Co-Authors: David Vicent, F. Malaisse-lagae, María Luisa Villanueva-peñacarrillo, Leclercq-meyer, Isabel Valverde, Willy Malaisse
    Abstract:

    Both the monomethyl and dimethyl esters of Succinic Acid, administered intravenously to fasted and anesthetized rats, caused a rapid increase in plasma insulin. A positive insulin secretory response to Succinic Acid monomethyl ester was also observed after intraperitoneal injection to fed and conscious rats. On a molar basis, stimulation of the insulin release, evoked by Succinic Acid esters, represented about twice that caused by D-glucose. It is speculated that Succinic Acid esters may be efficient insulin secretagogues even in those models of noninsulin-dependent diabetes characterized by a site-specific defect in the transport of D-glucose or in the early steps of its catabolism in the pancreatic B-cell.

Dirk Weuster-botz – One of the best experts on this subject based on the ideXlab platform.

  • New reactive extraction systems for separation of bio-Succinic Acid
    Bioprocess and Biosystems Engineering, 2011
    Co-Authors: Tanja Kurzrock, Dirk Weuster-botz
    Abstract:

    Biotechnologically produced Succinic Acid has the potential to displace maleic Acid and its uses and to become an important feedstock for the chemical industry. In addition to optimized production strains and fermentation processes, an efficient separation of Succinic Acid from the aqueous fermentation broth is indispensable to compete with the current petrochemical production processes. In this context, high molecular weight amines are known to be effective extractants for organic Acids. For this reason, as a first step of isolation and puripurification, the reactive extraction of Succinic Acid was studied by mixing aqueous Succinic Acid solutions with 448 different amine–solvent mixtures as extraction agents (mixer-settler studies). The extraction agents consist either of one amine and one solvent (208 reactive extraction systems) or two amines and two solvents (240 reactive extraction systems). Maximum extraction yields of Succinic Acid from an aqueous solution with 423 mM Succinic Acid at pH 2.0 were obtained with more than 95% yield with trihexylamine solved in 1-octanol or with dihexylamine and diisooctylamine solved in 1-octanol and 1-hexanol. Applying these optimized reactive extraction systems with Escherichia coli fermentation broth resulted in extraction yields of 78–85% due to the increased ionic strength of the fermentation supernatant and the co-extraction of other organic Acids (e.g., lactic Acid and acetic Acid), which represent typical fermentation byproducts.

  • Metabolic engineering of Saccharomyces cerevisiae for the biotechnological production of Succinic Acid.
    Metabolic engineering, 2010
    Co-Authors: Andreas Raab, Dirk Weuster-botz, Gabi Gebhardt, Natalia Bolotina, Christine Lang
    Abstract:

    Abstract The production of bio-based Succinic Acid is receiving great attention, and several predominantly prokaryotic organisms have been evaluated for this purpose. In this study we report on the suitability of the highly Acid– and osmotolerant yeast Saccharomyces cerevisiae as a Succinic Acid production host. We implemented a metabolic engineering strategy for the oxidative production of Succinic Acid in yeast by deletion of the genes SDH1, SDH2, IDH1 and IDP1. The engineered strains harbor a TCA cycle that is completely interrupted after the intermediates isocitrate and succinate. The strains show no serious growth constraints on glucose. In glucose-grown shake flasflask cultures, the quadruple deletion strain Δsdh1Δsdh2Δidh1Δidp1 produces Succinic Acid at a titer of 3.62 g L−1 (factor 4.8 compared to wild-type) at a yield of 0.11 mol (mol glucose)−1. Succinic Acid is not accumulated intracellularly. This makes the yeast S. cerevisiae a suitable and promising candidate for the biotechnological production of Succinic Acid on an industrial scale.

  • Recovery of Succinic Acid from fermentation broth.
    Biotechnol. Lett., 2010
    Co-Authors: Tanja Kurzrock, Dirk Weuster-botz
    Abstract:

    Succinic Acid is of high interest as bio-feedstock for the chemical industry. It is a precursor for a variety of many other chemicals, e.g. 1,4-butandiol, tetrahydrofuran, biodegradable polymers and fumaric Acid. Besides optimized production strains and fermentation processes it is indispensable to develop cost-saving and energy-effective downstream processes to compete with the current petrochemical production process. Various methods such as precipitation, sorption and ion exchange, electrodialysis, and liquid-liquid extraction have been investigated for the recovery of Succinic Acid from fermentation broth and are reviewed critically here.

Rosana L. Fialho – One of the best experts on this subject based on the ideXlab platform.

Carlos Pelayoortiz – One of the best experts on this subject based on the ideXlab platform.

  • kinetic study of Succinic Acid production by actinobacillus succinogenes zt 130
    Process Biochemistry, 2008
    Co-Authors: Rosa Isela Coronagonzalez, Andre Bories, V Gonzalezalvarez, Carlos Pelayoortiz
    Abstract:

    Abstract The effect of different glucose concentrations (10–100 g/l) on Succinic Acid production by Actinobacillus succinogenes was studied. The maximum Succinic Acid concentration obtained was 33.8 g/l from 54.7 g/l of glucose. Productivities, conversion yields, and specific rates decreased when the amount of initial glucose was increased. The growth stopped with 22 g/l of Acid mixture produced (Succinic, formic, and acetic Acids) and Succinic Acid production stopped with 45 g/l of Acid mixture produced. These results point to a double inhibitory effect by glucose and products on growth and Succinic Acid production. The inhibition phenomenon was adequately described by Jerusalimsky equations for specific rate of growth and specific rate of Succinic Acid production. These expressions helped to quantify substrate and product inhibition effects.

Hyohak Song – One of the best experts on this subject based on the ideXlab platform.

  • Recovery of Succinic Acid produced by fermentation of a metabolically engineered Mannheimia Succiniciproducens strain.
    Journal of biotechnology, 2007
    Co-Authors: Hyohak Song, Sang Yup Lee, Won Hi Hong, Yun Suk Huh, Yeon Ki Hong
    Abstract:

    There have recently been much advances in the production of Succinic Acid, an important four-carbon dicarboxylic Acid for many industrial applications, by fermentation of several natural and engineered bacterial strains. Mannheimia Succiniciproducens MBEL55E isolated from bovine rumen is able to produce Succinic Acid with high efficiency, but also produces acetic, formic and lactic Acids just like other anaerobic Succinic Acid producers. We recently reported the development of an engineered M. Succiniciproducens LPK7 strain which produces Succinic Acid as a major fermentation product while producing much reduced by-products. Having an improved Succinic Acid producer developed, it is equally important to develop a cost-effective downstream process for the recovery of Succinic Acid. In this paper, we report the development of a simpler and more efficient method for the recovery of Succinic Acid. For the recovery of Succinic Acid from the fermentation broth of LPK7 strain, a simple process composed of a single reactive extraction, vacuum distillation, and crystallization yielded highly purified Succinic Acid (greater than 99.5% purity, wt%) with a high yield of 67.05 wt%. When the same recovery process or even multiple reactive extraction steps were applied to the fermentation broth of MBEL55E, lower purity and yield of Succinic Acid were obtained. These results suggest that Succinic Acid can be purified in a cost-effective manner by using the fermentation broth of engineered LPK7 strain, showing the importance of integrating the strain development, fermentation and downstream process for optimizing the whole processes for Succinic Acid production.

  • production of Succinic Acid by bacterial fermentation
    Enzyme and Microbial Technology, 2006
    Co-Authors: Hyohak Song
    Abstract:

    Succinic Acid produced by various microorganisms can be used as a precursor of many industrially important chemicals in food, chemical and pharmaceutical industries. The assessment of raw material cost and the estimation of the potential market size clearly indicate that the current petroleum-based Succinic Acid process will be replaced by the fermentative Succinic Acid production system in the foreseeable future. This paper reviews processes for fermentative Succinic Acid production, especially focusing on the use of several promising Succinic Acid producers including Actinobacillus succinogenes, Anaerobiospirillum Succiniciproducens, Mannheimia Succiniciproducens and recombinant Escherichia coli. Processes for the recovery of Succinic Acid from fermentation broth are also reviewed briefly. Finally, we suggest further works required to improve the strain performance suitable for successful commercialization of fermentative Succinic Acid production.

  • Genome-Based Metabolic Engineering of Mannheimia Succiniciproducens for Succinic Acid Production
    Applied and environmental microbiology, 2006
    Co-Authors: Sang Jun Lee, Hyohak Song, Sang Yup Lee
    Abstract:

    Succinic Acid is a four-carbon dicarboxylic Acid produced as one of the fermentation products of anaerobic metametabolism. 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.