Succinic acid production pathway

Fig. 2 Succinic acid production pathway of A. succinogenes (1) PEP carboxykinase (2) malate dehydrogenase ...

Fig. 3 Succinic acid production pathways of E. coli (1) pyruvate-formate lyase (2) lactate dehydrogenase ...

Dharmadi et al. (2006) studied glycerol fermentation by E. coli at acidic pH and fonnd that ethanol accounted for 86% of all prodncts in the fermentation broth. A small percentage of succinic acid (7%) was also identified, this is because both ethanol and succinic acid production through glycerol fermentation is redox-balanced process (Fig. 8.4). However, compare with sncciiuc acid prodnction pathway, the reactions led to ethanol production have a net gain of one ATP per each molecule of... 

Pathway for succinic acid production from glucose by E. coli strain AFP111 (From Donnelly et al. (1998a), with permission)... 

Donnelly MI, Millard CS, Clark DP, Chen MJ, Rathke JW (1998a) A novel fermentation pathway in an Escherichia coli mutant producing succinic acid, acetic acid, and ethanol. Appl Biochem Biotechnol 70-72 187-198 Donnelly M, Millard CS, Stols L (1998b) Mutant E. coli strain with increased succinic acid production. US Patent 5,770,435... 

Diacids. The microbial generation of mahc, fumaric, and succinic acid essentially imphes Krebs cycle pathway engineering of biocatalytic organisms to overproduce oxaloacetate as the primary four-carbon diacid that subsequently undergoes reduction and dehydration processes (Scheme 2.9). The use of these four-carbon diacids as intermediate chemicals and the state of their desirable microbial production is briefly outlined. 

Succinic acid is commonly produced in microbes because it exists as a part of the TCA cycle, one of the ordinary metabolic pathways for production of energy. Several groups in the world are developing this production system to produce cheaper succinic acid from renewable resources like starch, glucose, cellulose and so on. If succinic acid could be produced from cheap carbon sources and the price were competitive with the petroleum-base product, many C4 chemicals could be expected as derivatives. 1,4-Butanediol is the typical one, which has a huge market. 

Some of the glucose is converted to D-lactic and to succinic acids (pathway/, Fig. 17-9) hence the name mixed acid fermentation. Table 17-1 gives typical yields of the mixed acid fermentation of E. coli. Among the four major products are acetate, ethanol, H2, and C02, as shown in Eq. 17-25. However, at high pH formate accumulated instead of C02. 

This -ketoadipate pathway produces e.g., succinic acid, a compound used as monomer for the production of aliphatic polyesters. Already in 1881, the production of e.g., 1,3-propanediol by the fermentation of glycerol was reported [8],... 

COs to form oxalacetate which under anaerobic conditions is reduced to malate. The malate in turn may be converted to fumarate and succinate (Fig, 5). The last step in this series of reactions is blocked by malonate. The second pathway involves the aerobic condensation of pyruvate and oxalacetate followed by oxidation of the condensation product to form -ketoglutarate and succinate. Wood has proposed that the first condensation product of the aerobic tricarboxylic cycle is cfs-aconitic acid which is then converted to succinate by way of isocitric, oxalosuccinic, and a-ketoglutaric acids. The a-ketoglutarate is decarboxylated and oxidized to succinic acid. Isotopic a-ketoglutarate containing isotopic carbon only in the carboxyl group located a to the carbonyl would be expected to yield non-isotopic succinate after decarboxylation. This accounts for the absence of isotopic carbon in succinate isolated from malonate-poisoned liver after incubation with pyruvate and isotopic bicarbonate. 

Under anaerobic conditions, the levels of Krebs cycle enzymes in yeast are greatly lowered. The question arises therefore as to how cells synthesize the organic acids (e.g. succinic, oxoglutaric, malic, oxaloacetic) essential for biosynthetic reactions and cell growth. Two mechanisms have been proposed, the first envisages a limited operation of the Krebs cycle with the oxidative formation of succinic acid, whereas the second involves the synthesis of additional enzymes leading to the production of succinate by a reductive pathway. 

In the reductive pathway, the Krebs cycle enzymes are assumed to operate as far as a-oxoglutarate, thus forming a linear pathway. A second linear pathway, from oxaloacetate to malate to fumarate to succinate, is suggested to account for the formation of succinic acid [46]. In support of this new pathway are the observations that (/) yeast contains cytoplasmic malate dehydrogenases capable of converting oxaloacetate to malate, (//) several fumarate reductases (FAD-dependent) have been found in the yeast cytoplasm which have high affinity for fumarate and are unable to oxidize succinate [52] and (Hi) succinate is a significant product of fermentation, i.e. an end product . 

In addition to ethanol and COg, (the main end products of the metabolism of maltose) and the minor product glycerol, several organic acids are also produced. Organic acids (e.g. citrate and succinate) are imporant in contributing to the sourness (acidity) of beer and several have distinctive tastes. The non-volatile acids include oxo-acids such as pyruvate and a-oxoglutarate which are excreted by yeast in their reduced forms lactate and 2-hydroxy-glutarate. Malic acid, the product of the carboxylation of pyruvate, and succinic acid, the end product of the reductive pathway from oxaloacetate (or formed via a restricted Krebs cycle. Fig. 17.11) are also excreted. 

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