Escherichia succinic acid

L Stols, G Kulkarni, BG Harris, MI Donnelly. Expression of Ascaris suum malic enzyme in a mutant Escherichia coli allows production of succinic acid from glucose. Appl Biochem Biotechnol 63-65 153-158, 1997. 

There is no current commercial biologic process for the production of succinic acid. In past laboratory systems, when succinic acid has been produced by fermentation, lime is added to the fermentation medium to neutralize the acid, yielding calcium succinate (2). The calcium succinate salt then precipitates out of the solution. Subsequently, sulfuric acid is added to the salt to produce the free soluble succinic acid and solid calcium sulfate (gypsum). The acid is then purified with several washings over a sorbent to remove impurities. The disposal of the solid waste is both a directly economic and an environmental concern, as is the cost of the raw materials. Some key process-related problems have been identified as follows (1) the separation of dilute product streams and the related costs of recovery, (2) the elimination of the salt waste from the current purification process, and (3) the reduction of inhibition to the product succinic acid on the fermentation itself. Acetic acid is also a byproduct of the fermentation of glucose by Anaerobiospirillium succiniciproducens almost 1 mol of acetate will be produced for every 2 mol of succinate (3). Under certain cultivation conditions by a mutant Escherichia coli, lesser amounts of acetate can be produced (4,5). This byproduct will also need to be separated. 

There has been considerable research over the past 5-10 yr dedicated to improving microorganisms and separations technologies in order to reduce the overall cost of biobased succinic acid, much of which has been cofunded by DOE. This research has resulted in the development of the fermentation microorganism Escherichia coli strain AFP111, which exhibits greatly improved productivity. Fermentation with AFP111 to produce succinic acid has recently been successfully tested at commercial scale. 

Oxyrase.. We must also consider the Oxyrase svstem for o.xvgen removal. This is presently derived from Escherichia coli or Bacillus subtil is, but could be derived from other sources too, such as various yeasts (J. Copeland, Oxyrase Inc., personal communication), making the system potentially suitable for use in foods. Because of the diversity of enzymes in this system, the presence of such substrates as lactic acid, succinic acid, formic acid, or a-glveerophosphate, tound in virtually any biological tissue, can effect deoxygenation and attendant stabilization or restriction on 1 he growth of aerobic oiganisms. 

Lee S J, Lee D-Y, Kim TY et al (2005) Metabolic engineering of Escherichia coli for enhanced production of succinic acid, based on genome comparison and in silico gene knockout simulation. Appl Environ Microbiol 71 7880-7887... 

Early experiments concerned the enzymatic hydrogenation of fumaric acid to succinic acid, catalyzed by either yeast 24,55 or enzyme extracts from yeast cells56. Much later, strains of Escherichia coli, Aerobacter aerogenes and Aerobacter cloacae were shown to have the same ability 57,58. An interesting mixed culture fermentation has been developed, where the fungus Rhizopus chinensis produces fumaric acid from glucose and a selected E. coli converts the previously formed fumaric acid into succinic acid58. 

The starting compounds for the biosynthesis of vanillic acid in genetically modified Escherichia coli are erythrose 4-phosphate and phosphoenol pyruvate. The erythrose is an intermediate product in carbohydrate metabolism (Calvin cycle, dark reaction of photosynthesis). [154, 155] Phosphoenol pyruvate is produced in several steps from 3-phosphoglyceric acid, or from a technical point of view, from succinic acid via the citric acid cycle. [156]... 

Agarwal L, Isar J, Meghwanshi GK, Saxena RK (2006) A cost effective fermentative production of succinic acid from cane molasses and com steep liquor by Escherichia coli. J Appl Microbiol 100 1348-1354... 

Andersson C, Hodge D, Berglund KA, Rova U. (2007). Effect of different carbon sources on the production of succinic acid using metabolically engineered Escherichia coli. Biotechnol Prog, 23, 381-388. 

Hong SH, Lee SY. (2001). Metabolic flux analysis for succinic acid production by recombinant Escherichia coli with amphfied malic enzyme activity. Biotechnol Bioeng, 74, 89-95. 

Hong SH, Lee SY. (2002). Importance of redox balance on the production of succinic acid by metabohcaUy engineered Escherichia coli. Appl Microbiol Biotechnol, 58, 286-290. 

Sanchez AM, Bennett GN, San KY. (2005a). Efficient succinic acid production from glucose through overexpression of pyruvate carboxylase in an Escherichia coli alcohol dehydrogenase and lactate dehydrogenase mutant. Biotechnol Prog, 21, 358-365. 

Vemuri GN, Eiteman MA, Altman E. (2002). Effects of growth mode and pyruvate carboxylase on succinic acid production by metabolically engineered strains of Escherichia coli. Appl Environ Microbiol, 68, 1715-1727. 

Succinic acid can be produced by anaerobic fermentation of several wild-type strains Anaerobiospirillum, Propionibacterium, Escherichia,Pec-tinas. Succinie aeid is eonsidered as one of the major bio-based platform ehemieals (Figure 1.9). Its applieations are foreseen as well in commodity chemicals (THF, hydrojgrsuccinimide etc.), as organic acids (malic, fumaric, itaconic etc.) or polymers (polybutylene succinate, PBS). ... 

Wang D, Li Q, Mao Y, Xing J, Su Z. High-level succinic acid production and yield by lactose-induced expression of phosphoenolpyruvate carboxylase in ptsG mutant Escherichia coli. Appl Microbiol Biotechnol 2010 87 2025-35. 

Dittrich CR, Bennett GN, San KY. Metabolic engineering of the anaerobic central metabolic pathway in Escherichia coli for the simultaneous anaerobic production of isoamyl acetate and succinic acid. Biotechnol Prog 2009 25 1304-9. 

Wu H, Li ZM, Zhou L,Ae Q. Improved succinic acid production in the anaerobic culture of an Escherichia coli pflB IdhA double mutant as a result of enhanced anaplerotic activities in the preceding aerobic culture. Appl Environ Microbiol 2007 73 7837-43. 

Liang L, Liu R,Wang G, Gou D, Ma J, Chen K, et al. Regulation of NAD (H) pool and NADH/ NAD ratio by overexpression of nicotinic acid phosphoribosyltransferase for succinic acid production in Escherichia coli NZNlll. Enzyme Microbiol Technol 2012 51 286-93. 

Millard, C.S., Chao, Y.-P., Liao, J.C., and Donnelly, M.I. (1996) Enhanced production of succinic acid by overexpression of phosphoenolpyruvate carboxylase in Escherichia coli. Appl. Environ. Microbiol, 62, 1808-1810. 

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