fumarates and propionic-acid

The review describes efforts toward metabolic engineering of production of organic acids. One aspect of the strategy involves the generation of an appropriate amount and type of reduced cofactor needed for the designed pathway. The ability to capture reducing power in the proper form, NADH or NADPH for the biosynthetic reactions leading to the organic acid, requires specific attention in designing the host and also depends on the feedstock used and cell energetic requirements for efficient metabolism during production. Recent work on the formation and commercial uses of a number of small mono- and diacids is discussed with redox differences, major biosynthetic precursors and engineering strategies outlined. Specific attention is given to those acids that are used in balancing cell redox or providing reduction equivalents for the cell, such as formate, which can be used in conjunction with metabolic engineering of other products to improve yields. Since a number of widely studied acids derived from oxaloacetate as an important precursor, several of these acids are covered with the general strategies and particular components summarized, including succinate, fumarate and malate. Since malate and fumarate are less reduced than succinate, the availability of reduction equivalents and level of aerobiosis are important parameters in optimizing production of these compounds in various hosts. Several other more oxidized acids are also discussed as in some cases, they may be desired products or their formation is minimized to afford higher yields of more reduced products. The placement and connections among acids in the typical central metabolic network are presented along with the use of a number of specific non-native enzymes to enhance routes to high production, where available alternative pathways and strategies are discussed. While many organic acids are derived from a few precursors within central metabolism, each organic acid has its own special requirements for high production and best compatibility with host physiology.

Topics: Carbon; Formates; Fumarates; Malates; Metabolic Engineering; Metabolic Networks and Pathways; Oxidation-Reduction; Propionates; Succinic Acid

The effect of organic acids and mannanoligosaccharide addition to the diet was assessed in pigs orally inoculated with Salmonella typhimurium. Forty-six growers were distributed among four treatments: Basal Diet (BD); BD+encapsulated organic acids; BD+free organic acids; BD+mannanoligosaccharide. Seroconversion was monitored, and feces and tissue samples were tested for Salmonella isolation. No treatment prevented the carrier state, but a tendency of lower fecal excretion was observed in the group treated with mannanoligosaccharide.

Topics: Animals; Carrier State; Citric Acid; Diet; Dietary Supplements; Feces; Formates; Fumarates; Malates; Mannans; Oligosaccharides; Phosphoric Acids; Propionates; Salmonella Infections, Animal; Salmonella typhimurium; Swine; Swine Diseases

Geobacter species in a phylogenetic cluster known as subsurface clade 1 are often the predominant microorganisms in subsurface environments in which Fe(III) reduction is the primary electron-accepting process. Geobacter bemidjiensis, a member of this clade, was isolated from hydrocarbon-contaminated subsurface sediments in Bemidji, Minnesota, and is closely related to Geobacter species found to be abundant at other subsurface sites. This study examines whether there are significant differences in the metabolism and physiology of G. bemidjiensis compared to non-subsurface Geobacter species.. Annotation of the genome sequence of G. bemidjiensis indicates several differences in metabolism compared to previously sequenced non-subsurface Geobacteraceae, which will be useful for in silico metabolic modeling of subsurface bioremediation processes involving Geobacter species. Pathways can now be predicted for the use of various carbon sources such as propionate by G. bemidjiensis. Additional metabolic capabilities such as carbon dioxide fixation and growth on glucose were predicted from the genome annotation. The presence of different dicarboxylic acid transporters and two oxaloacetate decarboxylases in G. bemidjiensis may explain its ability to grow by disproportionation of fumarate. Although benzoate is the only aromatic compound that G. bemidjiensis is known or predicted to utilize as an electron donor and carbon source, the genome suggests that this species may be able to detoxify other aromatic pollutants without degrading them. Furthermore, G. bemidjiensis is auxotrophic for 4-aminobenzoate, which makes it the first Geobacter species identified as having a vitamin requirement. Several features of the genome indicated that G. bemidjiensis has enhanced abilities to respire, detoxify and avoid oxygen.. Overall, the genome sequence of G. bemidjiensis offers surprising insights into the metabolism and physiology of Geobacteraceae in subsurface environments, compared to non-subsurface Geobacter species, such as the ability to disproportionate fumarate, more efficient oxidation of propionate, enhanced responses to oxygen stress, and dependence on the environment for a vitamin requirement. Therefore, an understanding of the activity of Geobacter species in the subsurface is more likely to benefit from studies of subsurface isolates such as G. bemidjiensis than from the non-subsurface model species studied so far.

Topics: Aldehyde Oxidoreductases; Biodegradation, Environmental; Carbohydrate Metabolism; Carbon Dioxide; Cell Wall; Electrons; Environmental Microbiology; Fatty Acids; Frameshift Mutation; Fumarates; Genes, Bacterial; Genome, Bacterial; Geobacter; Glucose; Iron; Metabolic Networks and Pathways; Multienzyme Complexes; Multigene Family; Osmosis; Oxidation-Reduction; Oxo-Acid-Lyases; Propionates; Pyruvic Acid; Species Specificity; Surface Properties

Two psychrophilic, Gram-negative, rod-shaped, motile bacteria (strains 112T and 102T) that conserved energy from dissimilatory Fe(III) reduction concomitant with acetate oxidation were isolated from permanently cold Arctic marine sediments. Both strains grew at temperatures down to -2 degrees C, with respective temperature optima of 14 degrees C and 14-17 degrees C for strains 112T and 102T. The isolated strains reduced Fe(III) using common fermentation products such as acetate, lactate, propionate, formate or hydrogen as electron donors, and they also grew with fumarate as the sole substrate. As alternatives to Fe(III), they reduced fumarate, S0 and Mn(IV). Based on 16S rRNA gene sequence similarity, strain 112T was most closely related to Desulfuromonas acetoxidans (97.0 %) and Desulfuromonas thiophila NZ27T (95.5 %), and strain 102T to Malonomonas rubra Gra Mal 1T (96.3 %) and Desulfuromusa succinoxidans GylacT (95.9 %) within the Deltaproteobacteria. Strains 112T and 102T therefore represent novel species, for which the names Desulfuromonas svalbardensis sp. nov. (type strain 112T=DSM 16958T=JCM 12927T) and Desulfuromusa ferrireducens sp. nov. (type strain 102T=DSM 16956T=JCM 12926T) are proposed.

Topics: Acetic Acid; Arctic Regions; Bacterial Typing Techniques; Deltaproteobacteria; Fatty Acids; Ferric Compounds; Formates; Fumarates; Genes, rRNA; Geologic Sediments; Hydrogen; Lactic Acid; Manganese; Microscopy, Electron; Molecular Sequence Data; Movement; Oxidation-Reduction; Phylogeny; Propionates; RNA, Bacterial; RNA, Ribosomal, 16S; Soil Microbiology; Sulfur

It has previously been suggested that organic acids enhance iron absorption. We have studied the effect of nine organic acids on the absorption of Fe(II) and Fe(III) in the human epithelial cell line Caco-2. The effect obtained was dose-dependent, and the greatest increase (43-fold) was observed for tartaric acid (4 mmol/L) on Fe(III) (10 micromol/L). Tartaric, malic, succinic, and fumaric acids enhanced Fe(II) and Fe(III) uptake. Citric and oxalic acid, on the other hand, inhibited Fe(II) uptake but enhanced Fe(III) uptake. Propionic and acetic acid increased the Fe(II) uptake, but had no effect on Fe(III) uptake. Our results show a correlation between absorption pattern and chemical structure; e.g. hydroxyl groups, in addition to carboxyls, were connected with a positive influence. The results may be important for elucidating factors affecting iron bioavailability in the small intestine and for the development of foods with improved iron bioavailability.

Topics: Absorption; Acetic Acid; Caco-2 Cells; Carboxylic Acids; Citric Acid; Ferric Compounds; Ferrous Compounds; Fumarates; Humans; Iron; Malates; Oxalic Acid; Propionates; Succinic Acid; Tartrates

Metabolism of [2-13C]-, [3-13C]-, and [1,2,3-13C]propionate in perfused rat livers and [2-13C]-acetate in perfused rat hearts has been examined in tissue extracts by 13C NMR. Label from [2-13C]-propionate was preferentially incorporated into the C2 carbon of lactate, alanine, and aspartate in liver tissue while label from [3-13C]propionate appeared preferentially in the C3 carbon of those same molecules. These data suggest that 13C may not be completely randomized in the symmetric citric acid cycle intermediates succinate and fumarate as is normally assumed but that some fraction of those intermediates may be transferred between enzymes in this span of the cycle with conservation of spatial orientation, consistent with recent results obtained in yeast [Sumegi et al. (1990) Biochemistry 29, 9106-9110]. This was confirmed by performing similar experiments with [1,2,3-13C]propionate. Time-dependent asymmetry was also observed between the intensities of the glutamate C2 and C3 resonances and between the aspartate C2 and C3 resonances in 13C NMR spectra of intact hearts and heart extracts during early perfusion with [2-13C]-acetate. A model is presented which predicts that isotopic asymmetry is observed only during the first 2-3 turns of the cycle pools when isotope enters the cycle via acetyl-CoA even if all symmetric cycle intermediates retain a unique molecular orientation on each pass through the citric acid cycle.

Topics: Acetates; Animals; Biological Transport; Carbon Isotopes; Citrates; Citric Acid; Citric Acid Cycle; Fumarates; Glutamates; Glutamic Acid; Lactates; Lactic Acid; Liver; Magnetic Resonance Spectroscopy; Myocardium; Propionates; Pyruvates; Pyruvic Acid; Rats; Succinates; Succinic Acid

Four growth experiments were conducted to assess the effects of organic acid supplementation on performance of starter and finisher pigs. Three 4-wk starter experiments utilized 392 pigs fed simple corn-soybean meal diets. A fourth experiment employed 135 finisher pigs in a 6-wk study. Each of the starter experiments was initiated immediately after weaning; piglets were 30 +/- 3 d of age. In Exp. 1, weanling pigs fed a 19% crude protein, simple corn-soybean meal diet were compared with pigs fed similar diets supplemented with 2% propionic, fumaric, or citric acid. Addition of each acid improved (P less than .07) efficiency of gain, while propionate depressed (P less than .05) feed intake. Additions of 1, 2, 3 or 4% fumarate were made in Exp. 2, resulting in linear daily gain and feed efficiency improvements (P less than .05). In Exp. 3, a possible protein-sparing effect of fumaric acid was investigated. Increasing protein levels from 16 to 20% improved daily gain (P less than .01) and feed efficiency (P less than .0001); fumarate supplementation (2%) increased (P less than .01) gain:feed. However, there was no protein X fumaric acid interaction. In Exp. 4, no treatment effects were noted with performance of finisher pigs fed a 14% crude protein, corn-soybean meal diet was compared with that of pigs fed similar diets supplemented with 1.5 or 3% fumaric acid.

Topics: Animals; Body Weight; Citrates; Citric Acid; Dietary Proteins; Energy Metabolism; Female; Food, Fortified; Fumarates; Glycine max; Hydrogen-Ion Concentration; Male; Propionates; Swine; Zea mays