Fumaric acid production by fermentation

Roa Engel CA, Straathof AJJ, Zijlmans TW, Van Guhk WM, van der Widen LAM. (2008). Fumaric acid production by fermentation. Appl Microbiol Biotechnol, 78, 379-389. 

Fumaric acid production by fermentation was operated in the United States during the 1940s (Goldberg et al. 2006) but later this process was discontinued and replaced by chemical synthesis from maleic anhydride. Maleic anhydride was originally... 

FIGURE 8.4 Reductive carboxylation pathway of fumaric acid biosynthesis. Adapted from Roa Engel, C.A., Strmthof, A.].]., Zijlmans, T.W., van Gulik, W.M., van der Wielen, L.A.M., 2008. Fumaric acid production by fermentation. Applied Microbiology and Biotechnology 78, 379-389. 

In the present study, we evaluated a two-step process for succinic acid production. The first process was fumaric acid production by Rhizopus sp. using rice bran, and the second process was succinic acid production by Enterococcus faecalis RKY1 (5-7) using fungal culture broth obtained in the first process. We investigated the effects of rice bran on fumaric acid production and optimized the culture medium for fumaric acid fermentation. Furthermore, we optimized the culture conditions for succinic acid conversion from fumaric acid produced by the first process. 

Fumaric acid production from starch hydrolysate by R. arrhizus NRRL 1526 was studied by Federici et al. [75] in a 3-1 stirred-tank fermentor with CaCO, and KOH/KCO3 as the neutralizing agent and CO2 source. The fermentation conditions for fumaric acid production by this fungus from potato flour has been optimized by Moresi et al. [76]. 

Roa Engel CA, van Gulik WM, Marang L, van der Widen LAM, Straathof AJJ. (2011). Development of a low pH fermentation strategy for fumaric acid production by Rhizopus... 

Fumaric acid was once produced on a commercial scale by fermentation using a fungal strain of Rhizopus arrhizus in the early 1940s. Later, biological production of fumaric acid was replaced by petrochemical processes, which were economically more attractive. Currently, fumaric acid is chemically synthesized from maleic anhydride (or maleic acid), obtained from butane oxidation. Nevertheless, maleic anhydride is a petroleum derivative that has increased in price because petroleum prices are rising quickly. As a result, there is renewed interest in fumaric acid production by using submerged fermentation. 

To optimize the culture medium for fumaric acid production, we investigated the effects of rice bran concentrations and various carbon sources. When rice bran was used as a nitrogen source, the effects of additional elements (phosphate, magnesium, zinc, and iron) on fumaric acid production were also investigated. The medium previously reported by Zhou et al. (11) was used as the basal medium. Fermentations were performed in 250-mL Erlenmeyer flasks containing 100 mL of medium. 

Rhizopus oryzae is an indispensable microorganism in industrial fermentation, as it is widely employed to produce L-lactic acid as well as other organic acids. This organism is able to produce only one stereospecific product (L-lactic acid), rather than a racemic mixture and can, therefore, fulfill the need for producing a food additive to be used as both acidulant and preservative. During L-lactic acid fermentation many other metabolites can be produced as by-products. These include fumaric acid, malic acid, ethanol, and the like. However, these metabolites can greatly influence the downstream process and the quality of the L(+)-lactic acid produced. Fumaric acid is the main by-product, as a result of a special metabolic pathway in L-lactic acid production by R. oryzae (Wang et al., 2005). 

Fumaric acid is among the top 12 chemicals produced by industrial fermentation. Due to a scarcity of petroleum worldwide, fermentation routes for fumaric acid production are gaining importance (Roa Engel et al., 2011). The fermentative production of these acids from renewable resources has received extensive attention worldwide and can replace fossil-based production via maleic acid (Deng et al., 2012). 

Fumaric add production can be increased by using the well-known producer Rhizopus strain, possessing high glucoamylase activity and maintaining conditions for mycelia growth for increased fumaric acid production af a reduced fermentation time. 

The conventional method for malic acid production is extraction from fruits. However, this method has no convenient application, owing to its low production capacity (Tsao et al., 1999). Malic acid can be chemically synthesized by the hydration of either maleic or fumaric acid. The enzymatic conversion of fumaric acid mediated by fumarase also permits malic acid production. The conversion of chemically derived fumaric acid to L-malic acid using fumarase (fumaratehydratase, EC 4.2.1.2) can be achieved by biological hydration or the fungal fermentation of simple sugars (Battat et al., 1991 Neufeld et al., 1991 Alberty, 1961). 

Fumaric acid is used in the plastics industry, in the food industry and as a source of malic add. Although demand has increased rapidly over the last 30 years its production from fermentation has been totally replaced by a chemical method. It is now produced far more cheaply by the catalytic oxidation of hydrocarbons, particularly benzene. With the continuing uncertainties concerning the availability and cost of petroleum, however, fermentation may yet be a viable alternative. 

Fumaric acid, a metabolite of many fungi, lichens moss and some plants, and mainly used as the diacid component in alkyd resins, is produced commercially to some extent by fermentation of glucose in Rhizopus arrhizus yet productivity improvements appear essential for the product to be an option for replacing its petrochemical production by catalytic isomerization of maleic acid. 

Carta, E. S. Soccol, C. R. Ramos, L. P. Fontana, J. D. Production of fumaric acid by fermentation of enzymic hydrolyzates derived from cassava bagasse, Bioresour. Technol, 1999, 68, 23-28. 

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