SUCCINIC ACID

SUCCINATE

CAS Number: 110-15-6
EC Number: 203-740-4
Chemical Formula: HOOCCH₂CH₂COOH
Molar Mass: 118.09 g/mol

Succinic acid is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2.
The name derives from Latin succinum, meaning amber. 

In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state.
Succinic acid is marketed as food additive E363. 
Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA). 

Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling.
As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. 
Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh syndrome, and Melas syndrome, and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury.

Succinic acid, a four-carbon diacid, has been the focus of many research projects aimed at developing more economically viable methods of fermenting sugar-containing natural materials. 
Succinic acid fermentation processes also consume CO2, thereby potentially contributing to reductions in CO2 emissions. 

Succinic acid could also become a commodity used as an intermediate in the chemical synthesis and manufacture of synthetic resins and biodegradable polymers. 
Much attention has been given recently to the use of microorganisms to produce succinic acid as an alternative to chemical synthesis. 

We have attempted to maximize succinic acid production by Actinobacillus succinogenes using an experimental design methodology for optimizing the concentrations of the medium components. 
The first experiment consisted of a 24−1 fractional factorial design, and the second entailed a Central Composite Rotational Design so as to achieve optimal conditions. 

The optimal concentrations of nutrients predicted by the model were: NaHCO3, 10.0 g l−1; MgSO4, 3.0 g l−1; yeast extract, 2.0 g l−1; KH2PO4. 
5.0 g l−1; these were experimentally validated.

Under the best conversion conditions, as determined by statistical analysis, the production of succinic acid was carried out in an instrumented bioreactor using sugarcane bagasse hemicellulose hydrolysate, yielding a concentration of 22.5 g l−1.
Succinic acid is a precursor of many important, large-volume industrial chemicals and consumer products. 

Succinic acidwas once common knowledge that many ruminant microorganisms accumulated succinic acid under anaerobic conditions. 
However, Succinic acid was not until the discovery of Anaerobiospirillum succiniciproducens at the Michigan Biotechnology Institute (MBI), which was capable of producing succinic acid up to about 50 g/L under optimum conditions, that the commercial feasibility of producing the compound by biological processes was realized. 

Other microbial strains capable of producing succinic acid to high final concentrations subsequently were isolated and engineered, followed by development of fermentation processes for their uses. 
Processes for recovery and purification of succinic acid from fermentation broths were simultaneously established along with new applications of succinic acid, e.g., production of biodegradable deicing compounds and solvents. 

Several technologies for the fermentation-based production of succinic acid and the subsequent conversion to useful products are currently commercialized. 
This review gives a summary of the development of microbial strains, their fermentation, and the importance of the down-stream recovery and purification efforts to suit various applications in the context of their current commercialization status for biologically derived succinic acid

Succinic acid, with molecular formulation C4H6O4, is a water-soluble, odorless, colorless crystal with an acid taste that is used as a chemical intermediate, in medicine, the manufacture of lacquers, and to make perfume esters. 
Succinic acid is also used in foods as a sequestrant, buffer, and a neutralizing agent. 
Succinic acid is a normal intermediary metabolite and a constituent of the citric acid cycle, and found naturally in human urine

Succinic Acid is distributed widely through the natural world, where Succinic acid is contained in bivalves, fossils, seaweed, lichen, bacteria and so on. 
Succinic acid was discovered in the year 1550 when Dr. Agricola with Germany distilled amber. 

"Succinic Acid" is useful, non-toxic, stable and harmless to the human body. 
Succinic acid is generated in a citric acid cycle (succinic acid dehydrate enzyme) and a succinic acid-glycine cycle through the process of metabolism and eventually becomes energy. 

Succinic Acid is industrially produced by hydrogenation of Maleic Anhydride. 
Succinic Acid of NIPPON SHOKUBAI has not only been used as food additives but also biodegradable polymers, bath additives, plating agents, photochemicals and so on

Succinic acid is a precursor of many important, large-volume industrial chemicals and consumer products. 
Succinic acid was once common knowledge that many ruminant microorganisms accumulated succinic acid under anaerobic conditions. 

However, Succinic acid was not until the discovery of Anaerobiospirillum succiniciproducens at the Michigan Biotechnology Institute (MBI), which was capable of producing succinic acid up to about 50 g/L under optimum conditions, that the commercial feasibility of producing the compound by biological processes was realized. 
Other microbial strains capable of producing succinic acid to high final concentrations subsequently were isolated and engineered, followed by development of fermentation processes for their uses. 

Processes for recovery and purification of succinic acid from fermentation broths were simultaneously established along with new applications of succinic acid, e.g., production of biodegradable deicing compounds and solvents. 
Several technologies for the fermentation-based production of succinic acid and the subsequent conversion to useful products are currently commercialized. 
This review gives a summary of the development of microbial strains, their fermentation, and the importance of the down-stream recovery and purification efforts to suit various applications in the context of their current commercialization status for biologically derived succinic acid.

Succinic acid is an alpha,omega-dicarboxylic acid resulting from the formal oxidation of each of the terminal methyl groups of butane to the corresponding carboxy group. 
Succinic acid is an intermediate metabolite in the citric acid cycle. 

Succinic acid has a role as a nutraceutical, a radiation protective agent, an anti-ulcer drug, a micronutrient and a fundamental metabolite. 
Succinic acid is an alpha,omega-dicarboxylic acid, a C4-dicarboxylic acid and a lipid. 
Succinic acid is a conjugate acid of a succinate

Succinic acid accounts for up to the 90% of the nonvolatile acids produced during alcoholic fermentation. 
The content of this acid in wine ranges normally from 0.5 to 1.5 g/L, but the maximum concentration may reach 3 g/L. 

Succinic acid is a diprotic acid. 
Succinic acid pKa at 25°C are 4.21 and 5.64. 
This means that at pH 3.50, most succinic acid (83.9%) is present in Succinic acid undissociated form; monodissociated succinate ion accounts only for approximately 16%, while the dissociation of the second carboxylic group is practically negligible

Succinic acid, an organic acid is an important building block that has a wide range of synthetic applications. 
Presently Succinic acid is synthesized from petrochemical compounds. 

Due to Succinic acid increasing demand many bio-based methods have been proposed for Succinic acid synthesis as an efficient alternative. 
Succinic acids utility as a low shrinkage additive (LSA) in unsaturated polyester resin (UPR) has been investigated.

Succinic acid (COOH(CH2)2COOH) is a carboxylic acid used in food (as an acidulant), pharmaceutical (as anexcipient), personal care (soaps) and chemical (pesticides, dyes and lacquers) industries. 
Bio-based succinic acid is seen as an important platform chemical for the production of biodegradable plastics and as a substitute of several chemicals (such as adipic acid)

Succinic acid was traditionally produced synthetically from fossil oil or by an expensive distillation of amber. 
During the last decade, new methods of production through biotechnological processes have been developed industrially (so-called bio-succinic acid). 
Looking for more natural ingredients, the cosmetics market now has access to a new affordable plant-based ingredient.

Succinic acid is an aliphatic dicarboxylic acid (diacid) described by the empirical formula C4H6O4, and is naturally found in living organisms. 
This diacid is one entry pathway into the Krebs cycle that takes place inside the mitochondria found in all cells in the human body. 

Succinic acid provides energy required for the organism to function and is therefore involved in a variety of important biological actions.
Widely used in the food industry as a chelating agent and as a pH adjuster, succinic acid has been recognized as a safe substance for years. 

Studies also proved Succinic acid antioxidant properties especially for cosmetics. 
Succinic acid is also a fully safe intermediate to manufacture derivatives like emollients, surfactants and emulsifiers used in cosmetic formulations.

Succinic acid is a naturally occurring ingredient in amber and sugar cane as well as apple cider vinegar, and is found in living organisms. 
The process of fermentation obtains succinic acid sustainably.

While Succinic acid has only recently become a 'buzzy' ingredient in skincare, succinic has been around for a while.

Succinic acid works by helping to peel away dead skin cells from pores to keep them clear.
Succinic acid is used to target blemishes, heal scarring, and improve signs of ageing, and Succinic acid is most often likened to salicylic acid. 

Unlike salicylic, however, "it doesn’t encourage a lot of exfoliation," notes Rock. 
For this reason, Succinic acid not really comparable to stronger acids that encourage rapid exfoliation and skin turnover.

Succinic acid is a white, odorless solid with a highly acidic taste.
In an aqueous solution, succinic acid readily ionizes to form Succinic acid conjugate base, succinate. 

As a diprotic acid, succinic acid undergoes two successive deprotonation reactions:
(CH2)2(CO2H)2 → (CH2)2(CO2H)(CO2)− + H+
(CH2)2(CO2H)(CO2)− → (CH2)2(CO2)22− + H+

The pKa of these processes are 4.3 and 5.6, respectively. 
Both anions are colorless and can be isolated as the salts, e.g., Na(CH2)2(CO2H)(CO2) and Na2(CH2)2(CO2)2. 
In living organisms, primarily succinate, not succinic acid, is found. 

As a radical group Succinic acid is called a succinyl group. 
Like most simple mono- and dicarboxylic acids, Succinic acid is not harmful but can be an irritant to skin and eyes.

Historically, succinic acid was obtained from amber by distillation and has thus been known as spirit of amber. 
Common industrial routes include hydrogenation of maleic acid, oxidation of 1,4-butanediol, and carbonylation of ethylene glycol. 

Succinate is also produced from butane via maleic anhydride.
Global production is estimated at 16,000 to 30,000 tons a year, with an annual growth rate of 10%. 

Genetically engineered Escherichia coli and Saccharomyces cerevisiae are proposed for the commercial production via fermentation of glucose

Succinic acid can be dehydrogenated to fumaric acid or be converted to diesters, such as diethylsuccinate (CH2CO2CH2CH3)2. 
This diethyl ester is a substrate in the Stobbe condensation. 

Dehydration of succinic acid gives succinic anhydride.
Succinate can be used to derive 1,4-butanediol, maleic anhydride, succinimide, 2-pyrrolidinone and tetrahydrofuran

Succinic acid is registered under the REACH Regulation and is manufactured in and / or imported to the European Economic Area, at ≥ 10 000 to < 100 000 tonnes per annum.
Succinic acid is used by consumers, by professional workers (widespread uses), in formulation or re-packing, at industrial sites and in manufacturing.

Succinic acid, also called Butanedioic Acid, a dicarboxylic acid of molecular formula C4H6O4 that is widely distributed in almost all plant and animal tissues and that plays a significant role in intermediary metabolism. 
Succinic acid is a colourless crystalline solid, soluble in water, with a melting point of 185–187° C (365–369° F).

Succinic acid is a precursor to some polyesters and a component of some alkyd resins.
Succinic acid) can be synthesized using succinic acid as a precursor.

The automotive and electronics industries heavily rely on BDO to produce connectors, insulators, wheel covers, gearshift knobs and reinforcing beams.
Succinic acid also serves as the bases of certain biodegradable polymers, which are of interest in tissue engineering applications. 

Acylation with succinic acid is called succination. 
Oversuccination occurs when more than one succinate adds to a substrate

As a food additive and dietary supplement, succinic acid is generally recognized as safe by the U.S. Food and Drug Administration.
Succinic acid is used primarily as an acidity regulator in the food and beverage industry. 

Succinic acid is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste.
As an excipient in pharmaceutical products, Succinic acid is also used to control acidity  or as a counter ion.
Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate.

The Succinic Acid (Succinate) assay kit is suitable for the specific assay of succinic acid in wine, cheese, eggs, sauce and other food products.

Succinic acid (or succinate) is found in all plant and animal materials as a result of the central metabolic role played by this dicarboxylic acid in the Citric Acid Cycle. 
Succinic acid concentrations are monitored in the manufacture of numerous foodstuffs and beverages, including wine, soy sauce, soy bean flour, fruit juice and dairy products (e.g. cheese).

Succinic acid (butanedioic acid) is a dicarboxylic acid. 
Succinic acid is a common intermediate in the metabolic pathway of several anaerobic and facultative micro-organisms.

Succinic acid is used as a dietary supplement for symptoms related to menopause such as hot flashes and irritability. 
Succinic acid is used as a flavoring agent for food and beverages. 

Succinic acid is used to manufacture polyurethanes, paints and coatings, adhesives, sealants, artificial leathers, cosmetics and personal care products, biodegradable plastics, nylons, industrial lubricants, phthalate-free plasticizers, and dyes & pigments. 
In the pharmaceutical industry, Succinic acid is used in the preparation of active calcium succinate, as a starting material for active pharmaceutical ingredients (adipic acid, N-methyl pyrrolidinone, 2-pyrrolidinone, succinate salts, etc.), as an additive in drug formation, for medicines of sedative, antispasmer, antiplegm, antiphogistic, anrhoter, contraception and cancer curing, in the preparation of vitamin A and anti-Inflammatory, and as antidote for toxic substance.

Succinic acid may be used in the following processes:
As a leaching agent in extracting lithium (Li), cobalt from used Li-ion batteries and magnesium from magnesite ore.
Synthesis of new elastic polyesters.

As a cocrystallising agent in the synthesis of cocrystals with organic molecules.
Succinic acid (succinate) is a dicarboxylic acid. 

Succinic acid is an important component of the citric acid or TCA cycle and is capable of donating electrons to the electron transfer chain. 
Succinate is found in all living organisms ranging from bacteria to plants to mammals. 

In eukaryotes, succinate is generated in the mitochondria via the tricarboxylic acid cycle (TCA). 
Succinate can readily be imported into the mitochondrial matrix by the n-butylmalonate- (or phenylsuccinate-) sensitive dicarboxylate carrier in exchange with inorganic phosphate or another organic acid, e. g. malate. 

Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space. 
Succinate has multiple biological roles including roles as a metabolic intermediate and roles as a cell signalling molecule. 

Succinate can alter gene expression patterns, thereby modulating the epigenetic landscape or Succinic acid can exhibit hormone-like signaling functions. 
As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. 

Succinate can be broken down or metabolized into fumarate by the enzyme succinate dehydrogenase (SDH), which is part of the electron transport chain involved in making ATP. 
Dysregulation of succinate synthesis, and therefore ATP synthesis, can happen in a number of genetic mitochondrial diseases, such as Leigh syndrome, and Melas syndrome. 

Succinate has been found to be associated with D-2-hydroxyglutaric aciduria, which is an inborn error of metabolism. 
Succinic acid has recently been identified as an oncometabolite or an endogenous, cancer causing metabolite. 

High levels of this organic acid can be found in tumors or biofluids surrounding tumors. 
Succinic acids oncogenic action appears to due to Succinic acid ability to inhibit prolyl hydroxylase-containing enzymes. 

In many tumours, oxygen availability becomes limited (hypoxia) very quickly due to rapid cell proliferation and limited blood vessel growth. 
The major regulator of the response to hypoxia is the HIF transcription factor (HIF-alpha). 
Under normal oxygen levels, protein levels of HIF-alpha are very low due to constant degradation, mediated by a series of post-translational modification events catalyzed by the prolyl hydroxylase domain-containing enzymes PHD1, 2 and 3, that hydroxylate HIF-alpha and lead to Succinic acid degradation.

Biotechnological Applications of Succinic acid:
Succinic acid and its derivatives are used as flavoring agents for food and beverages. 
This acid could be used as feedstock for dyes, insecticides, perfumes, lacquers, as well as in the manufacture of clothing, paint, links, and fibers. 

Succinic acid is widely used in medicine as an antistress, antihypoxic, and immunity-improving agent, in animal diets, and as a stimulator of plant growth. 
Succinic acid is also a component of bio-based polymers such as nylons or polyesters. 

Succinate esters are precursors for the known petrochemical products such as 1,4-butanediol, tetrahydrofuran, c-butyrolactone, and various pyrrolidinone derivatives.
Succinic acid production was reported for the first time when Succinic acid was grown on ethanol under aerobic conditions and nitrogen limitation. 

Succinic acid amount was 63.4 g/L as the major product of batch fermentation in this process. 
However, the disadvantage was low yield of succinic acid on ethanol (58 %), and a high cost of production.

The concentration of succinic acid and Succinic acid yield were found to be 38.8 g/L and 82.45 % of n-alkane consumed, respectively.
Succinic acid production was also studied by genetically modified strains using glucose and glycerol as substrates. 

Constructed temperaturesensitive mutant strains with mutations in the succinate dehydrogenase encoding gene SDH1 by in vitro mutagenesis-based approach. 
Then, the mutants were used to optimize the composition of the media for selection of transformants with the deletion in the SDH2 gene. 
The defects of each succinate dehydrogenase subunit prevented the growth on glucose, but the mutant strains grew on glycerol and produced succinate in the presence of the buffering agent CaCO3. 

Subsequent selection of the strain with deleted SDH2 gene for increased viability was allowed to obtain a strain that is capable to accumulate succinate at the level of more than 450 g/L with buffering and more than 17 g/L without buffering. 
Therefore, a reduced succinate dehydrogenase activity can lead to an increased succinate production

Able to produce succinic acid at low pH values. 
High amounts of succinate can be achieved by genetic engineering.

Uses of Succinic acid:
Found in fossils, fungi, and lichens.
Present in nearly all plant and animal tissues.

Succinic acid is used to make lacquers, dyes, esters for perfumes, alkyd resins, pharmaceuticals, plasticizers, lubricants, and pesticides.
Also used in photography, as a sequestrant in foods, a buffering and neutralizing agent, for radiation dosimetry, and to promote plant growth and increased yields in food crops.

Organic synthesis, manufacture of lacquers, dyes esters for perfumes, photography, in foods as sequestrant, buffer, neutralizing agent

Uses of succinic acid range from scientific applications such as radiation dosimetry and standard buffer solutions to applications in agriculture, food, medicine, plastics, cosmetics, textiles, plating, and waste-gas scrubbing

Succinic acid is used as starting material in the manufacture of alkyd resins, dyes, pharmaceuticals, and pesticides. 
Reaction with glycols gives polyesters; esters formed by reaction with monoalcohols are important plasticizers and lubricants.

In the growing of food, Succinic acid is a biogenic stimulant leading to faster plant growth and increased yields.

Succinic acid (COOH(CH2)2COOH) is a carboxylic acid used in food (as an acidulant), pharmaceutical (as an excipient), personal care (soaps) and chemical (pesticides, dyes and lacquers) industries. 
Bio-based succinic acid is seen as an important platform chemical for the production of biodegradable plastics and as a substitute of several chemicals (such as adipic acid).

Succinic Acid is widely used in the food industry as a chelating agent and as a pH adjuster. 
The FDA has granted Succinic Acid with the GRAS status (Generally Recognised as Safe Substance). 

Studies conducted within the food industry show Succinic Acid has anti-oxidant properties: even though this does not imply the same will be exerted when Succinic acid is applied topically, Succinic acid gives an indication that suitable tests could be carried out to understand whether Succinic Acid maintain such effect once formulated in a cosmetic product. 
Succinic Acid is also used as an intermediate to manufacture several chemicals, amongst which raw materials for the cosmetic and personal-care industry, e.g. emollients, surfactants and emulsifiers.

Succinic acid is widely use as organic intermediates for the pharmaceutical, engineering plastics, resins etc.
For the synthesis of sedatives, contraceptives and cancer drugs in the pharmaceutical industry. 
In the chemical industry for the production of dyes, alkyd resin, glass fiber reinforced plastics, ion exchange resins and pesticides.

Succinic Acid is an acidulant that is commercially prepared by the hydrogenation of maleic or fumaric acid. 
Succinic acid is a nonhygroscopic acid but is more soluble in 25°c water than fumaric and adipic acid.

Succinic acid has low acid strength and slow taste build-up; Succinic acid is not a substitute for normal acidulants. 
Succinic acid combines with proteins in modifying the plasticity of bread dough. 
Succinic acid functions as an acidulant and flavor enhancer in relishes, beverages, and hot sausages.

Succinic Acid was identified in essential oil from Saxifraga stolonifera and has antibacterial activity.

Consumer Uses of Succinic acid:
Succinic acid is used in the following products: adsorbents, fertilisers, inks and toners, washing & cleaning products, water softeners, adhesives and sealants, coating products, fillers, putties, plasters, modelling clay, perfumes and fragrances, pharmaceuticals, polymers and cosmetics and personal care products.
Other release to the environment of Succinic acid is likely to occur from: indoor use (e.g. machine wash liquids/detergents, automotive care products, paints and coating or adhesives, fragrances and air fresheners) and outdoor use.

Adhesives and sealants,
Water treatment products.

Widespread uses by professional workers of Succinic acid:
Succinic acid is used in the following products: pH regulators and water treatment products, anti-freeze products, metal surface treatment products, heat transfer fluids, hydraulic fluids, washing & cleaning products, fertilisers, water softeners and cosmetics and personal care products. 
Succinic acid is used in the following areas: printing and recorded media reproduction, health services and scientific research and development. 

Succinic acid is used for the manufacture of: and plastic products. 
Other release to the environment of Succinic acid is likely to occur from: indoor use (e.g. machine wash liquids/detergents, automotive care products, paints and coating or adhesives, fragrances and air fresheners), outdoor use and outdoor use in close systems with minimal release (e.g. hydraulic liquids in automotive suspension, lubricants in motor oil and break fluids).

Uses at industrial sites of Succinic acid:
Succinic acid is used in the following products: pH regulators and water treatment products, metal surface treatment products, leather treatment products, metal working fluids and laboratory chemicals.
Succinic acid is used in the following areas: municipal supply (e.g. electricity, steam, gas, water) and sewage treatment and scientific research and development.

Succinic acid is used for the manufacture of: chemicals, plastic products and textile, leather or fur.
Release to the environment of Succinic acid can occur from industrial use: in processing aids at industrial sites, as an intermediate step in further manufacturing of another substance (use of intermediates), for thermoplastic manufacture, in the production of articles and as processing aid.

Adsorbents and absorbents,
Corrosion inhibitors and anti-scaling agents,
Intermediates,
Plasticizers,
Processing aids, not otherwise listed.

Chemical Properties of Succinic acid:
Succinic acid is a normal constituent of almost all plant and animal tissues. 
Succinic anhydride is the dehydration product of the acid. 

Succinic acid was first obtained as the distillate from amber (Latin, Succinum) for which Succinic acid is named. 
Succinic acid occurs in beet, brocoli, rhubarb, sauerkraut, cheese, meat, molasses, eggs, peat, coal, fruits, honey, and urine. 

Succinic acid is formed by the chemical and biochemical oxidation of fats, by alcoholic fermentation of sugar, and in numerous catalyzed oxidation processes. 
Succinic acid is also a major byproduct in the manufacture of adipic acid.

Succinic acid, a dicarboxylic acid, is a relatively new nonhygroscopic product approved for food uses. 
Succinic acid apparent taste characteristics in foods appear to be very similar to the other acidulants of this type, although pure aqueous solutions tend to have a slightly bitter taste. 
Succinic anhydride, in contrast, is the only commercially available anhydride for food uses.

Succinic acid,C02H(CH2)2C02H, also known as butanedioic acid,butane diacid, and amber acid, is a colorless odorless prisms or white crystalline powder that melts at 185°C (364 of). 
Soluble in water and alcohol, Succinic acid is used as a chemical intermediate, Succinic acid is used in lacquers,medicine,dyes,and as a taste modifier.

Biotechnological Production of Succinic acid:
Traditionally, succinic acid is produced by petrochemical synthesis using the precursor maleic acid. 
However, there are some microorganisms that are able to produce succinic acid. 

Maximum product concentrations of 106 g.L-1 with a yield of 1.25 mol of succinic acid per mole of glucose and a productivity of 1.36 g.L-1.h-1 have been achieved by growing A. succinogenes on glucose. 
A high productivity of 10.40 g.L-1.h-1 has been reached with A. succinogenes growing on a complex medium with glucose in a continuous process with an integrated membrane bioreactor-electrodialysis process. 

In this process, the product concentration has been 83 g.L-1. 
Moreover, metabolic engineering methods were used to develop strains with high productivity and titer as well as low byproduct formation. 

For example, growing C. glutamicum strain DldhA-pCRA717 on a defined medium with glucose, a high productivity of 11.80 g.L-1.h-1 with a yield of 1.37 mol of succinic acid per mole of glucose and a titer of 83 g.L-1 has been reported after 7 h. 
An extended cultivation resulted in a product concentration of 146 g.L-1 after 46 h.

Biochem/physiol Actions of Succinic acid:
Succinic acid is a byproduct of anaerobic fermentation in microbes. 
Succinic acid is a dicarboxylic acid and an intermediate in Kreb′s cycle. 

Polymorphism in succinate dehydrogenase leads to succinate accumulation. 
High levels of succinate impairs 2-oxoglutarate epigenetic signalling. 

Succinate levels may modulate tumor progression. 
Succinate inhibits histone demethylation and may contribute to epigenetic changes. 
Succinate is crucial for interleukin-1 β (IL-1β) synthesis during inflammation and immune signalling.

Human Metabolite Information of Succinic acid:

Tissue Locations of Succinic acid:
Adipose Tissue
Brain
Fibroblasts
Kidney
Liver
Pancreas
Placenta
Prostate
Skeletal Muscle
Spleen

Cellular Locations of Succinic acid:
Endoplasmic reticulum
Extracellular
Mitochondria
Peroxisome

Occurrence of Succinic acid:
Succinic acid is found in all plant and animal materials as a result of the central metabolic role played by this dicarboxylic acid in the Citric Acid Cycle. 
Succinic acid concentrations are monitored in the manufacture of numerous foodstuffs and beverages, including wine, soy sauce, soy bean flour, fruit juice and dairy products (e.g. cheese). 

The ripening process of apples can be followed by monitoring the falling levels of succinic acid. 
The occurrence of > 5 mg/kg of this acid in egg and egg products is indicative of microbial contamination. 

Apart from use as a flavouring agent in the food and beverage industries, succinic acid finds many other non-food applications, such as in the production of dyes, drugs, perfumes, lacquers, photographic chemicals and coolants.
Succinic acid is widely distributed in almost all plants, animals and microorganisms where Succinic acid is a common intermediate in the intermediary metabolism. 

A way to utilise this is with fermentation of biomass by microorganisms. 
Succinic acid is therefore a good candidate for biobased industrial production. 

A concept for a large scale production plant is patented by the company Diversified Natural Products. 
The plant consists of a fermentation stage and a separation stage. 
During the separations the succinate produced in the fermenter is crystallised to the final product, succinic acid.

Preparation of Succinic acid:
Succinic acid can also be manufactured by catalytic hydrogenation of malic or fumaric acids. 
Succinic acid has also been produced commercially by aqueous acid or alkalihydrolysis of succinonitrile derived from ethylene bromide and potassium cyanide.

Today succinic acid is mainly produced from fossil resources through maleic acid hydrogenation. 
Succinic acid can also be produced through fermentation of sugars. 
In that case, in addition to succinic acid, other carboxylic acids (such as lactic acid, formic acid, propionic acid) and alcohols (such as ethanol) are also obtained.

Reactivity Profile of Succinic acid:
Succinic acid reacts exothermically to neutralize bases, both organic and inorganic. 
Can react with active metals to form gaseous hydrogen and a metal salt. 

Such reactions are slow in the dry, but systems may absorb water from the air to allow corrosion of iron, steel, and aluminum parts and containers. 
Reacts slowly with cyanide salts to generate gaseous hydrogen cyanide. 

Reacts with solutions of cyanides to cause the release of gaseous hydrogen cyanide. 
May generate flammable and/or toxic gases and heat with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. 

May react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. 
Can be oxidized exothermically by strong oxidizing agents and reduced by strong reducing agents. 
May initiate polymerization reactions.

Methods of Manufacturing of Succinic acid:
Hydrogenation of maleic acid, maleic anhydride, or fumaric acid produces good yields of succinic acid.
1,4-Butanediol can be oxidized to succinic acid in several ways: (1) with O2 in an aqueous solution of an alkaline-earth hydroxide at 90-110 °C in the presence of Pd-C; (2) by ozonolysis in aqueous acetic acid; or (3) by reaction with N2O4 at low temperature.

Succinic acid can be obtained by phase-transfer-catalyzed reaction of 2-haloacetates, electrolytic dimerization of bromoacetic acid or ester, oxidation of 3-cyanopropanal, and fermentation of n-alkanes.
Succinic acid is derived from fermentation of ammonium tartrate.

Manufacture of Succinic acid:
Release to the environment of Succinic acid can occur from industrial use: manufacturing of Succinic acid.

General Manufacturing Information of Succinic acid:

Industry Processing Sectors:
All other basic organic chemical manufacturing
Plastic material and resin manufacturing
Utilities

Formulation or re-packing of Succinic acid:
Succinic acid is used in the following products: washing & cleaning products, water softeners, cosmetics and personal care products, non-metal-surface treatment products, inks and toners, paper chemicals and dyes and polymers.
Release to the environment of Succinic acid can occur from industrial use: formulation of mixtures.

Handling and Storage of Succinic acid:

Nonfire Spill Response:
SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. 
Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. 

Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. 
Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. 

Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. 
STORAGE PRECAUTIONS: You should store this chemical under refrigerated temperatures, and keep Succinic acid away from oxidizing materials.

Storage Conditions of Succinic acid:
Keep tightly closed.

Safety Profile of Succinic acid:
Moderately toxic by subcutaneous route. 
A severe eye irritant. 

Mutation data reported. 
When heated to decomposition Succinic acid emits acrid smoke and irritating fumes.

First Aid of Succinic acid:
EYES: First check the victim for contact lenses and remove if present. 
Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. 

Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. 
IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. 

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. 
Gently wash all affected skin areas thoroughly with soap and water. 
If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. 

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. 
If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. 

Provide proper respiratory protection to rescuers entering an unknown atmosphere. 
Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. 

INGESTION: DO NOT INDUCE VOMITING. 
If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. 

Be prepared to transport the victim to a hospital if advised by a physician. 
If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. 

DO NOT INDUCE VOMITING. 
IMMEDIATELY transport the victim to a hospital.

Fire Fighting of Succinic acid:
Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher.

Accidental Release Measures of Succinic acid:

Disposal Methods of Succinic acid:
The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 
Recycle any unused portion of the material for Succinic acid approved use or return Succinic acid to the manufacturer or supplier. 
Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. 
Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Incineration: Succinic acid should be combined with paper or other flammable material. 
An alternate procedure is to dissolve Succinic acid in a flammable solvent and spray the solutions into the fire chamber.

Preventive Measures of Succinic acid:
The scientific literature for the use of contact lenses in industry is conflicting. 
The benefit or detrimental effects of wearing contact lenses depend not only upon Succinic acid, but also on factors including the form of Succinic acid, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. 

However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. 
In those specific cases, contact lenses should not be worn. 
In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Identifiers of Succinic acid:
CAS number: 110-15-6
EC number: 203-740-4
Grade: ChP,NF,JPE,ACS
Hill Formula: C₄H₆O₄
Chemical formula: HOOCCH₂CH₂COOH
Molar Mass: 118.09 g/mol
HS Code: 2917 19 80

Properties of Succinic acid:
Molecular Weight: 118.09
XLogP3: -0.6
Hydrogen Bond Donor Count: 2
Hydrogen Bond Acceptor Count: 4
Rotatable Bond Count: 3
Exact Mass: 118.02660867
Monoisotopic Mass: 118.02660867
Topological Polar Surface Area: 74.6 Ų
Heavy Atom Count: 8
Formal Charge: 0
Complexity: 92.6
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Specifications of Succinic acid:
Boiling point: 235 °C (1013 hPa)
Density:1.57 g/cm3 (25 °C)
Ignition  temperature: 470 °C
Melting Point: 188 °C
pH value: 2.7 (10 g/l, H₂O, 20 °C)
Bulk density: 940 kg/m3
Solubility: 58 g/l

Assay (alkalimetric) : 99.0 - 100.5 %
Assay (HPLC) : 99.0 - 100.5 %
Identity (IR) : passes test
Identity (HPLC)    : passes test
Identity (wet chemistry) : passes test
In water insoluble matter : ≤ 0.01 %
Melting range (lower value) : ≥ 185.0 °C
Melting range (upper value) : ≤ 190.0 °C
Melting point : 185.0 - 190.0 °C
Chloride (Cl) : ≤ 0.001 %
Phosphate (PO₄)    : ≤ 0.001 %
Sulfate (SO₄) : ≤ 0.003 %
Heavy metals (as Pb) : ≤ 0.0020 %
Heavy metals (as Pb) (ACS) : ≤ 5 ppm
Nitrogen compounds (as N) : ≤ 0.001 %
Fe (Iron) : ≤ 5 ppm
As (Arsenic) : ≤ 0.00015 %
Substances reducing permanganate : conforms
Residual solvents (ICH Q3C) : excluded by production process
Sulfated ash (600 °C) : ≤ 0.02 %

Regulatory process names of Succinic acid:
1,2-Ethanedicarboxylic acid
1,4-Butanedioic acid
Acidum succinicum
Amber acid
Asuccin
Bernsteinsaure
Butandisaeure
Dihydrofumaric acid
DL-Malic acid
Ethylene dicarboxylic acid
Ethylenesuccinic acid
Katasuccin
Kyselina jantarova
Succinate
Succinic acid
Succinic acid
succinic acid
Succinicum acidum
Wormwood acid

CAS names of Succinic acid:
Butanedioic acid

IUPAC names of Succinic acid:
1,4-Butanedioic acid
Butanedioic Acid
Butanedioic acid
butanedioic acid
Butanedionic acid
Registration dossier
Ethanedicarboxylic acid
Succinic
SUCCINIC ACID
Succinic Acid
Succinic acid
succinic acid
Succinic Acid
Succinic acid
succinic acid
1,4-Butanedioic acid
Butanedioic Acid
Butanedioic acid
butanedioic aci
Butanedionic acid
Ethanedicarboxylic acid
Succinic

Trade names of Succinic acid:
Biosuccinium™
Succinic acid
Succinic Acid 99,7

Other identifiers of Succinic acid:
110-15-6
2087491-34-5
2087491-34-5
623158-99-6
623158-99-6

Synonyms of Succinic acid:
1,2-Ethanedicarboxylic acid
1,4-Butanedioic acid
110-15-6
203-740-4
4-02-00-01908
Acide butanedioique
Acide succinique
Acido succinico
ácido succínico
Ácido succínico
succinic acid
butanedioic acid
110-15-6
Amber acid
Asuccin
Wormwood acid
Dihydrofumaric acid
Katasuccin
Bernsteinsaure
ethylenesuccinic acid
1,2-Ethanedicarboxylic acid
1,4-Butanedioic acid
Wormwood
Butandisaeure
Acidum succinicum
Butanedionic acid
Succinicum acidum
Kyselina jantarova
Butane diacid
Ethylene dicarboxylic acid
Spirit of amber
Bernsteinsaure
Kyselina jantarova
Ammonium succinate
HSDB 791
succinic-acid
UNII-AB6MNQ6J6L
MFCD00002789
succ
NSC 106449
AI3-06297
AB6MNQ6J6L
Butanedioic acid, homopolymer
E363
CHEBI:15741
C4-beta-polymorph
NSC25949
NSC-106449
NCGC00159372-02
NCGC00159372-04
Succinellite
acide succinique
Sal succini
Acid of amber
DSSTox_CID_3602
WLN: QV2VQ
DSSTox_RID_77102
DSSTox_GSID_23602
SIN
Ethylene succinic acid
Ethanedicarboxylic acid
Bernsteinsaeure
sodium succinate (anhydrous)
succinate, 9
acide butanedioique
26776-24-9
CAS-110-15-6
Succinic acid
Succinic acid (8CI)
Butanedioic acid (9CI)
EINECS 203-740-4
BRN 1754069
Dihydrofumarate
Succinicate
Butanedioic acid diammonium salt
Salt of amber
1cze
Butanedioic acid?
Nat.Succinic Acid
1,4-Butanedioate
Succinic acid, 6
Succinic acid, FCC
Succinic Acide,(S)
Succinic Acid (SA)
1,4-Butandioic Acid
Succinic acid, 99%
Succinic acid, natural
4lh2
1,2-Ethanedicarboxylate
Substrate analogue, 11
suc
Succinic acid, ACS grade
bmse000183
bmse000968
CHEMBL576
EC 203-740-4
HOOC-CH2-CH2-COOH
A 12084
4-02-00-01908
GTPL3637
DTXSID6023602
FEMA NO. 4719
BDBM26121
Succinic acid (Butanedioic acid)
HMS3885O04
ZINC895030
HY-N0420
STR02803
Tox21_111612
Tox21_201918
Tox21_303247
BBL002473
LMFA01170043
NSC-25949
NSC106449
s3791
STK387105
Succinic acid, >=99%, FCC, FG
Succinic acid, BioXtra, >=99.0%
AKOS000118899
Tox21_111612_1
CCG-266069
DB00139
LS40373
MCULE-5889111640
SuccinicAcid(IndustrialGrade&FoodGrade)
NCGC00159372-03
NCGC00159372-05
NCGC00159372-06
NCGC00257092-01
NCGC00259467-01
Succinic acid, ACS reagent, >=99.0%
BP-21128
I847
Succinic acid, ReagentPlus(R), >=99.0%
CS-0008946
FT-0652509
FT-0773657
N1941
S0100
Succinic acid, p.a., ACS reagent, 99.0%
Succinic acid, SAJ first grade, >=99.0%
SUCCINIC ACID HIGH PURITY GRADE 2.5KG
Succinic acid, purum p.a., >=99.0% (T)
Succinic acid, SAJ special grade, >=99.5%
1,4-BUTANEDIOIC ACID (SUCCINIC ACID)
A14596
C00042
D85169
Succinic acid, Vetec(TM) reagent grade, 98%
AB01332192-02
Q213050
SR-01000944556
J-002386
SR-01000944556-2
Z57127453
F2191-0239
37E8FFFB-70DA-4399-B724-476BD8715EF0
Succinic acid, certified reference material, TraceCERT(R)
Succinic acid, puriss. p.a., ACS reagent, >=99.5% (T)
Succinic acid, United States Pharmacopeia (USP) Reference Standard
Succinic acid, matrix substance for MALDI-MS, >=99.5% (T), Ultra pure
Succinic acid, anhydrous, free-flowing, Redi-Dri(TM), ACS reagent, >=99.0%
Succinic acid, BioReagent, suitable for cell culture, suitable for insect cell culture
Succinic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
1,2-Ethanedicarboxylic acid
1,4-Butanedioic acid
110-15-6
203-740-4
4-02-00-01908
Acide butanedioique
Acide succinique
Acido succinico 
ácido succínico
Ácido succínico
acidum succinicum 
Bernsteinsaeure
Bernsteinsäure
Butanedioic acid
HOOC-CH2-CH2-COOH
Kyselina jantarova
MFCD00002789
QV2VQ
Succinic acid
Succinic acid
Янтарная кислота 
14493-42-6
152556-05-3
21668-90-6 
61128-08-3
acidum succinicum
amber acid
asuccin
Bernsteinsaeure
Bernsteinsaure
Butandisaeure
BUTANE DIACID
BUTANEDIOICACID
CpeE protein
DB00139
Dihydrofumaric acid
Ethanedicarboxylic acid
Ethylene dicarboxylic acid
Ethylene succinic acid
FMR
fum
Fumaric acid
hydron
Katasuccin
Kyselina jantarova
MAE
Maleic acid
Sal succini
STR02803
Succinellite
succinic acid(free acid)
SUCCINIC-D4 ACID
succunic acide
Wormwood acid