Is it possible to produce succinic acid at a low pH?

Abstract

Bio-based succinate is still a matter of special emphasis in biotechnology and adjacent research areas. The vast majority of natural and engineered producers are bacterial strains that accumulate succinate under anaerobic conditions. Recently, we succeeded in obtaining an aerobic yeast strain capable of producing succinic acid at low pH. Herein, we discuss some difficulties and advantages of microbial pathways producing "succinic acid" rather than "succinate." It was concluded that the peculiar properties of the constructed yeast strain could be clarified in view of a distorted energy balance. There is evidence that in an acidic environment, the majority of the cellular energy available as ATP will be spent for proton and anion efflux. The decreased ATP:ADP ratio could essentially reduce the growth rate or even completely inhibit growth. In the same way, the preference of this elaborated strain for certain carbon sources could be explained in terms of energy balance. Nevertheless, the opportunity to exclude alkali and mineral acid waste from microbial succinate production seems environmentally friendly and cost-effective.

The production of succinic acid by yeast Yarrowia lipolytica through a two-step process

“…The use of a three-stage pH-shift technology during the growth and the biosynthesis phases is a principal approach for the development of highly effective and environmentally friendly processes of the α-ketoglutaric acid production. In this case, the calculated value of KOH expenditure was only 250 g per 1 kg of SA, while Yuzbashev et al (2011) reported that for the production of 1 ton of succinate with the use of bacteria, about half a ton of alkali (KOH) needs to be added to maintain neutral pH. According to literature data, the yeast Y. lipolytica can efficiently grow in a wide range of pH and produce practically valuable metabolites at low pH values (Zinjarde 2014).…”

“…This stage made up 60-70 % of the product cost (Zeikus et al 1999). It is considered that the promising process should imply the fermentation without any titration agent or with its limited use where the free SA is the main product (Yuzbashev et al 2011). However, the traditional producers of SA, bacteria A. succiniciproducens, A. succinogenes, M. succiniciproducens, recombinant strains of E. coli, and C. glutamicum, should be cultivated at neutral pH, since at lower pH (5-6), significant amounts of by-products (acetate, formate, ethanol, and others) are accumulated (Zeikus et al 1999;Carole et al 2004;Werpy et al 2006;McKinlay et al 2007;Bechthold et al 2008;Bozell and Petersen 2010;Cheng To maintain optimal pH value, it is necessary to add KOH, NaOH, and other bases which react with SA; as a result, SA salts are produced rather than the desired free SA; therefore, additional stage of medium acidifying was required before the SA extraction.…”

“…The SA production is mostly based on the use of bacteria, such as Anaerobiospirillum succiniciproducens, Actinobacillus succinogenes, Mannheimia succiniciproducens, Escherichia coli, and Corynebacterium glutamicum (Zeikus et al 1999;Carole et al 2004;Werpy et al 2006;McKinlay et al 2007;Bechthold et al 2008;Sauer et al 2008;Bozell and Petersen 2010;Cheng et al 2012). The pilot plants producing SA are known to operate in Europe, USA, and Japan for the last few years (Yuzbashev et al 2011;De Jong et al 2012). The SA had been also produced by fungus Penicillium simplicissimum (Gallmetzer et al 2002) and yeasts Saccharomyces cerevisiae (Arikawa et al 1999), Candida brumptii (Sato et al 1972), Candida zeylanoides (Mandeva et al 1981;Kamzolova et al 2009a), Candida catenulata (Kamzolova et al 2009a), and Yarrowia lipolytica (Yuzbashev et al 2010).…”

Continuous succinic acid fermentation by Actinobacillus succinogenes

“…These four companies plan to produce SA in excess of 150,000 tons per annum by the end of 2015 [3,4].…”

Succinic Acid: Technology Development and Commercialization

“…Saccharomyces cerevisiae, or other yeasts such as Yarrowia, can thrive under slightly acidic conditions and methods for their metabolic engineering are well established [33]. S. cerevisiae is an industrial organism capable of fermentative production and tolerance of high sugar concentrations.…”