Biotechnol Lett (2010) 32:331–339

DOI 10.1007/s10529-009-0163-6

REVIEW

Recovery of succinic acid from fermentation broth

Tanja Kurzrock • Dirk Weuster-Botz

Received: 9 June 2009 / Revised: 9 October 2009 / Accepted: 9 October 2009 / Published online: 8 November 2009
Ó Springer Science+Business Media B.V. 2009

Abstract Succinic acid is of high interest as bio- resins, dyestuffs, and pharmaceuticals and as additive
feedstock for the chemical industry. It is a precursor in the food industry (Cornils et al. 2005).
for a variety of many other chemicals, e.g. 1,4-butan- Nowadays, succinic acid is exclusively pro-
diol, tetrahydrofuran, biodegradable polymers and duced from crude oil by catalytic hydrogenation of
fumaric acid. Besides optimized production strains maleic anhydride to succinic anhydride and subse-
and fermentation processes it is indispensable to quent hydration or by direct catalytic hydrogenation
develop cost-saving and energy-effective downstream of maleic acid (Cornils and Lappe 2002). The market
processes to compete with the current petrochemical price of petrochemically produced succinic acid is
production process. Various methods such as precip- about US $ 5.9–8.8 kg-1 depending on its purity
itation, sorption and ion exchange, electrodialysis, and whereas the raw material costs based on production
liquid–liquid extraction have been investigated for the from maleic anhydride are about US $ 1 kg-1
recovery of succinic acid from fermentation broth and succinic acid (Song and Lee 2005).
are reviewed critically here. The current production of chemicals based on
succinic acid accounts to about 16.000 t/y (Patel
Keywords Electrodialysis
Ion exchange
2006). However the market potential is estimated to
Precipitation
Reactive extraction
be about 270,000 t/y if succinic acid replaced maleic
Succinic acid anhydride for all uses of the latter (Delhomme et al.
2009, Wilke and Vorlop 2004, Zeikus et al. 1999).
Because of these predictions and the rising oil price
interest in succinic acid production by fermentation
Introduction
processes is increasing.
Various working groups are dealing with the fermen-
Succinic acid, a dicarboxylic acid with four carbon
tation of succinic acid with strains of Anaerobiospiril-
atoms, plays an important role as a precursor
lum succiniciproducens, Actinobacillus succinogenes,
molecule for the synthesis of biodegradable polyester
Mannheimia succinici-producens, recombinant Esche-
richia coli strains and Corynebacterium glutamicum
(Bechthold et al. 2008, Okino et al. 2008), which all are
T. Kurzrock
D. Weuster-Botz (&) able to generate succinic acid under physiological
Institute of Biochemical Engineering, Technische
conditions in the presence of glucose and CO2. Succinic
Universität München, Boltzmannstr. 15, 85748 Garching,
Germany acid concentrations in the fermentation broth are reported
e-mail: [email protected] to be up to 146 g succinic acid l-1 (Okino et al. 2008).

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The raw material costs based on succinic acid production oxide. Lactic and citric acid have been recovered
via fermentation with glucose as carbon source are about industrially with this method (Vickroy 1985; Kirk–
US $ 0.43 kg-1 succinic acid (Song and Lee 2005). Othmer 1979). Moreover, some patents are concerned
For the biotechnological process to be competitive specifically with the precipitation of succinic acid
with petrochemical production it is necessary to with calcium hydroxide although these processes are
minimize the production costs. About 60% of the only at laboratory scale (Datta 1992; Datta et al.
total production costs are generated by downstream 1992; Berglund et al. 1991).
processing, e.g. the isolation and the purification of After addition of calcium hydroxide or calcium
the product in the fermentation broth (Bechthold et al. oxide, the calcium salt of succinic acid is filtered off
2008). For this reason, some new as well as some from the fermentation broth and then treated with
well known methods have been investigated for the concentrated sulfuric acid. In this way, the by-product
recovery of succinic acid. calcium sulfate (CaSO4), gypsum, is generated in an
The first downstream processing step is cell sepa- equimolar amount. The free succinic acid is purified
ration by centrifugal separation or microfiltration, by some commonly applied methods, e.g. active
usually followed by ultrafiltration to separate cell carbon or ion exchange and then the product is
debris, proteins and other polymers from the fermen- further concentrated and crystallized by evaporation.
tation supernatant. For the isolation and concentration With this approach, the crystallization of the acid is
of succinic acid many unit operations have been reported to be difficult and yields are low (Kertes and
suggested: precipitation with ammonia or calcium King 1985) (Fig. 1).
hydroxide, membrane processes such as electrodialy- A fermentation process with Anaerobiospirillum
sis, liquid–liquid extraction such as predispersed succiniciproducens yields 1.4 mol succinic acid per
solvent extraction with colloidal liquid aphrons or mol glucose. After precipitation with calcium
reactive extraction. Different sorption/ion exchange hydroxide the yield of succinic acid is 1.2 mol per
methods and crystallization are the methods of choice mol glucose, which already means a loss of nearly
for the final purification of the isolated acid. 15% of the acid has occurred (Datta 1992; Datta et al.
All of these unit operations are presented below and 1992). The complete process is depicted in Fig. 2.
their advantages and disadvantages will be discussed Besides this, the main disadvantage of precipita-
briefly with respect to their possible application for the tion with calcium hydroxide or calcium oxide is the
industrial recovery of succinic acid from fermentation high amount of the by-product calcium sulfate which
broth. cannot be used commercially because of smell and
colour impurities. Disposal of this by-product is
required. Another negative issue is the high con-
Ultrafiltration sumption of calcium hydroxide, calcium oxide and
sulfuric acid. These additives cannot be regenerated
Most unit-operations for the isolation of succinic acid or recycled, which results in high process costs (Datta
require ultrafiltration for the separation of cell-debris 1992; Datta et al. 1992). These are the reasons why
and proteins as a first step. The fermentation broth is precipitation with calcium hydroxide or calcium
directed through a bypass crossflow, hollow-fiber oxide is unlikely to be applied on an industrial scale
ultrafiltration unit and recirculated into the bioreactor for recovery of bio-succinic acid and is generally not
(Rüffer et al. 2004). considered viable for large-scale production (Her-
mann and Patel 2007).

Precipitation Precipitation with ammonia

Precipitation with calcium hydroxide Precipitation with ammonia is possible but so far has
only been described on a laboratory scale (Berglund
The classical industrial method for the isolation of et al. 1999; Yedur et al. 2001). In this case diammo-
carboxylic acids from an aqueous fermentation broth nium succinate is generated by controlling the pH of
is a precipitation with calcium hydroxide or calcium the fermentation broth with an ammonia-based

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Cellulose COOR
CONH2
COOR
CONH2
Fermentation Succinate
O
(esters) Succinamide
HO COOH HOOC NH2
- +
NH COO K
NH2
COOH COOH
O - +

Malic acid
COO K
Fumaric acid Succinimide Succinate (salts) 1,4-diaminobutane

CN
O O
COOH COOR CN
O O
Succiononitrile
COOH COOR
O O
Maleic acid Maleic Succinic Succinic acid O
anhydride anhydride
NH
O
2-Pyrrolidone
O N CH3
HO COOH OH
O O
O
OH
NMP CH2
HO COOH
N
Tartaric acid THF γ -Butyrolactone 1,4-Butanediol
NVP

Fig. 1 Map of routes to succinic based products

titration agent or by substituting the cation in the electrodialysis for downstream processing of succinic
succinate salt with ammonia after fermentation. The acid has been studied on a laboratory scale in recent
diammonium salt of succinic acid in the ultrafiltrated years. Glassner et al. (1992) proposed a desalting
fermentation broth is then treated with sulfate ions or electrodialysis combined with a water-splitting elec-
by combining it with ammonium bisulfate and/or trodialysis to achieve succinic acid with high purity
sulfuric acid at low pH to yield the succinic acid (Fig. 3). In a first purification step, the desalting
precipitate and ammonium sulfate. The by-product electrodialysis separates the ionic species, such as
ammonium sulfate can be cracked thermally into acids, from the non-ionic species, e.g. sugars, sac-
ammonia and ammonium bisulfate. The precipitated charides or proteins under an electric potential. The
succinic acid is separated and purified after dissolution desalting membranes are charged either with positive
in methanol and re-crystallisation. With this approach, or negative groups and selectively allow the cations
succinic acid can be refined with a yield of 93.3% or anions to pass through the membranes, e.g. the
based on the diammonium succinate available in the positively charged membranes allow the passage of
fermentation broth (Yedur et al. 2001). succinate anions and repel sodium cations. By this
The advantages of the integrated precipitation with mechanism all charged molecules pass through the
ammonia are the lower amount of waste by-products membrane whereas the uncharged molecules are not
and the possibility of recycling base and acid. The main influenced by the charge and the electric field. A
disadvantage is the low selectivity of the precipitation yield of 77% of succinic acid was achieved after
with ammonia. Other organic acids present in the electrodialysis.
fermentation broth will be precipitated together with In the next step the concentrated ionic stream
succinic acid at the same time (Yedur et al. 2001). with succinate and other ions is pumped across a
set of chelating ion-exchange columns to replace
the divalent cations of the succinate salt with
Electrodialysis sodium ions. The concentrated sodium succinate
solution with the undesired ions is then fed to a
Electrodialysis is a well known method in the food bipolar membrane water-splitting dialysis to obtain
industry for the separation of citric acid from citric succinic acid from succinate. This bipolar mem-
juices (Zang et al. 1966). The application of brane is able to split water into protons and

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Fig. 3 Process with electrodialysis and water-splitting electro-

dialysis

Disadvantages of electrodialysis are the high

energy consumption, the material costs of the mem-
branes and the low selectivity for succinic acid. Other
organic acids, e.g. acetic acid, are indeed isolated
Fig. 2 Precipitation process with calcium hydroxide
together with succinic acid (McKinlay et al. 2007).
Another problem is the presence of binary ions,
hydroxyl ions. Under an electric potential the which cannot be handled with electrodialysis mem-
succinate anions migrate to the anode and the branes. For this reason, fermentations neutralized
sodium ions to the cathode. The sodium ions react with magnesium or calcium hydroxide cannot be
with the hydroxyl ions to sodium hydroxide and acidified and purified (Zeikus et al. 1999). Fouling is
succinate reacts with the protons to succinic acid. another hitherto unsolved problem (Jaquet et al.
After water-splitting electrodialysis a total purifica- 1999).
tion yield of 60% was achieved; this means a loss
of 40% of the initial succinic acid. To yield a
higher purity ([99%) of succinic acid the aqueous Liquid–liquid extraction
solution is subjected to anionic and cationic ion
exchangers to remove ionic impurities. Liquid–liquid extraction itself is a well and exten-
The last step after electrodialysis and ion exchange sively used method in the chemical industry. There
is evaporation of water and thereby crystallization of has been a lot of research in the last 30 years on its
the succinic acid (Zeikus et al. 1999; Glassner et al. application for the separation of fermentation-based
1992; Berglund et al. 1991). products, e.g. carboxylic acids (King and Dtarr 1990;

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King and Sanchez 1985; King and Poole 1993). But in agents for the extraction of carboxylic acids (Lee
spite of these efforts liquid–liquid extraction is not et al. 2008; Yang et al. 1991; Kertes and King 1985).
usually applied in industrial production processes In the literature mostly simple reactive extraction
because most conventional extraction agents show systems with tertiary amines in alcohol, xylene,
very unfavourable distribution coefficients for organic heptane, kerosene, methylenchloride or nitrobenzene
acids. are described for the extraction of succinic acid from
an aqueous solution (Hong and Hong 2000a, b, c;
Reactive extraction Juang et al. 1997; Tung and King 1994a; Yang et al.
1991, Song et al. 2007). For example, Song et al.
To increase the extraction yield and the selectivity of (2007) proposed a simple process of reactive extrac-
the liquid–liquid extraction of organic acids from an tion with trioctylamine in 1-octanol, vacuum distil-
aqueous phase, many authors propose the use of lation and crystallization. In this approach, succinic
amines as reactive components, dissolved in non- acid has been isolated via reactive extraction with an
water miscible organic solvents. Amines offer a high extraction yield of more than 99% of the microbially
affinity to react with negatively charged molecules produced acid.
because of their high basicity (electron donor). A few complex systems have also been described:
Therefore they are suitable for the extraction of a mixture of amines in a mixture of solvents, e.g.
organic acids such as succinic acid (Pazouki and tripropylamine/trioctylamine or trialkylamines in
Panda 1998). The amine reacts with the succinic acid 1-octanol or chloroform and heptane (Hong and Hong
molecules at the interface between the aqueous and the 2000c; Heyberger et al. 1997). Matsumoto studied the
organic phase leading to the formation of amine-acid– extraction of organic acids using a combination of
complexes. These complexes are solubilized into the amine-based extractants and phosphorus-based ex-
organic phase. The mechanism consists in proton tractants (Matsumoto et al. 2001).
transfer or ion pair formation depending on the type of Reactive extraction with aliphatic amines depends
amine and the organic solvent (Kertes and King 1985; on the pH in the aqueous phase, the temperature, the
Hong et al. 2001). type and properties of the organic solvent and the
Tamada et al. (1990; Tamada and King 1990a, b) amine, the distribution coefficient, the loading ratio,
studied the reaction mechanism of reactive extraction the complexation equilibrium constant and the acid
of various carboxylic acids with Alamine 336—a concentration (Huh et al. 2004; Kahya et al. 2001).
mixture of trioctylamine and tridecylamine—in var- Most of the studies published so far on reactive
ious solvents. They distinguished 1,1-complexes extraction were performed with pure aqueous phases
(generated in active solvents like alcohol) and 2,1- and the organic acid apart from the study of Jun et al.
or 3,1-acid–amine-complexes (generated in inactive (2007). Jun et al. claimed that for an efficient reactive
solvents like alkanes or ketones). extraction of succinic acid with tertiary amines the
For the reactive extraction of succinic acid from an pH of the fermentation broth should be far below
aqueous phase, long-chain aliphatic primary, second- pKa1 = 4.2 so that most of the acid molecules are in
ary and tertiary amines are proposed (Tung and King the undissociated form. Impurities like other organic
1994a; Hong and Hong 2000a, b, c; Hong et al. 2002, acids and salts (HPO42-, PO43-, CO32-, SO42-)
Hong et al. 2004; Song et al. 2007). cause a decrease in extraction yield because of their
Primary amines are characterized by a high ionic strength. Their concentration should be mini-
solubility in the aqueous phase. Secondary amines mized in the upstream process. Therefore, an opposite
have the highest distribution coefficients but tend to approach was investigated by Huh et al. (2006). By-
form amides in the downstream regeneration by product acids and impurities like acetic acid, pyruvic
distillation. Only the undissociated acid can be acid and salts are removed from fermentation broth in
extracted by primary, secondary and tertiary amines. a pre-treatment step of reactive extraction with
In contrast, quaternary amines can extract the disso- trioctylamine. Residual glucose is removed by crys-
ciated and the undissociated form of the acid, but tallization at low pH. After the reactive extraction
they are difficult to regenerate by back extraction. step, succinic acid remains in the fermentation
Consequently, tertiary amines are the most attractive supernatant with a yield of 97.1% related to the

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initial amount. The final purification with an evapo- Predispersed solvent extraction (PDSE)
rative crystallizer leads to a purity of 99.8% of the
acid and an overall yield of 71.3%. This has been Conventional solvent extraction processes, such
shown in an experiment with Mannheimia succinic- as reactive extraction and back-extraction require
iproducens fermentation broth (Huh et al. 2006). energy consuming mixer-settler setups for mechani-
Reactive extraction on a laboratory scale is usually cal mixing and separation of the phases.
performed with simple mixer-settler setups such as Predispersed solvent extraction (PDSE) using col-
liquid–liquid centrifuges. Liquid–liquid centrifugal loidal liquid aphrons (CLAs) may be a new and more
extractors are well established for phase separation in energy-saving way for solvent extraction. The advan-
industry and they can easily be scaled up. In general tage of this approach is that less energy is necessary for
the amine solvent mixture can be recycled after back- phase mixing and separation. The extraction only
extraction with trimethylamine or pH-swing-, dilu- depends on the dispersion of the CLAs in the aqueous
ent-swing-, or temperature-swing-regeneration meth- fermentation broth. CLAs are defined as liquid glob-
ods of the organic acid (Tung and King 1994b; Poole ules with colloidal dimension encapsulated by an
and King 1991; Hong et al. 2001). The complete aqueous soapy shell and dispersed in a continuous
process scheme, not yet realized on an industrial aqueous phase. The liquid core contains a small
scale, is shown in Fig. 4. amount of oil soluble surfactant. An organic phase
Reactive extraction is generally considered to be (solvent with amine) is placed inside. Continuous
an effective primary separation step for the recovery operation with PDSE is carried out with succinic acid
of carboxylic acids from aqueous solutions (Cascaval aqueous solution as continuous phase and the CLAs as
and Balaction 2004). Furthermore reactive extraction dispersed phase in the column. The principle is a
enables the integrated product recovery of carboxylic counter current extraction in which the continuous
acids during fermentation (Rüffer et al. 2004). If the phase is supplied from the top of the column and the
separation process enables the recycling of the costly dispersed phase from the bottom – both with the same
amines efficiently, it is very likely that optimized flow rate. The stripping of the extracted succinic acid
reactive extraction processes may be applied in the from the organic phase is performed by temperature-
near future for industrial production of bio-succinic swing, pH-swing or diluent-swing.
acid. There should be no difference in extraction
capabilities between a PDSE process with CLAs
and a conventional mixer-settler extraction. The
extractability of the acid with CLAs and the stability
of the CLAs depend on the presence of salts, the
concentration of amines and solvents and the pH.
However, PDSE is less energy-consuming and for
this reason may be more cost-saving compared to a
standard reactive extraction process with centrifugal
extractors and has already been applied successfully
to real fermentation broth on a laboratory scale (Kim
et al. 2002; 2004a, b).

Sorption and ion exchange

After the separation of cells and proteins and the

isolation and concentration of the product some more
purification steps are necessary. Ion exchange is a well
established unit operation for the final purification of
succinic acid from an aqueous solution. Ion exchange
Fig. 4 Reactive extraction process for succinic acid is mainly applied for the removal of residual cations

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and anions. Kushiku proposes H-type strongly acidic byproducts (acetic acid, pyruvic acid and others) in
cation-exchange resins to produce succinic acid from the fermentation should be reduced to a minimum by
succinate. The concentration of hydrogen ions has to metabolic design of the microbial producers and
be 1–10% higher than the equivalent concentration of optimization of the fermentation processes.
the cations in the fermentation broth. Finally crystal- Separation processes based on reactive extraction
lization is applied to produce the pure succinic acid have been presented in a number of studies and
(Kushiku et al. 2006). patents as a cost-saving and environmentally friendly
Li et al. (2008) investigated an alkaline anion- approach for the recovery of succinic acid if all
exchange resin (NERCB 04) for in situ separation of additives, e.g. amines and solvents can be recycled. A
succinic acid from fermentation broth. The hydroxyl fermentation process integrated reactive extraction of
group of the acid reacts with the alkaline anion- succinic acid seems feasible. The efficiency of the
exchange resin whereas the resin acts as in situ base extraction depends on the type of amine and solvent,
producer at the same time. Thus base addition for pH- the pH in the fermentation broth, other acids and ions
control was reduced during the fermentation process. and the concentration of succinic acid itself. The
The elution of the acid and the regeneration of the extraction conditions and amine-solvent mixtures
resin are carried out by adding 0.5 M NaOH. have to be adapted to the different fermentation
A new approach was published by Jun et al. processes.
(2007). They suggested the use of mesoporous silica To compete with the present petrochemical pro-
(SBA-15) functionalized with primary, secondary and duction of succinic acid it is necessary to minimize the
tertiary amino-functional silanes for the isolation of total production costs. Hermann and Patel (2007)
pyruvic and succinic acid from fermentation broth. estimated the production costs plus profit of bio-
The amino-functionalized silanes are covalently succinic acid as function of the sugar price to 1.1–1.6 €
bound to the active layer of pore walls. The amine- kg-1 succinic acid (about US $ 1.6–2.4 kg-1 succinic
acid-complex is coupled via hydrogen bonding. acid) on 100,000 tons per year basis without giving
Pyruvic acid was adsorbed threefold better than further details on the downstream processing. They
succinic acid. Therefore, amino-functionalized SBA- expect that ‘‘in the future’’ these biotechnological
15 silica seems to be more useful for the removal of production costs plus profit can be reduced to 0.45–
contaminant acids from fermentation broth than for 0.92 € kg-1 succinic acid (about US $ 0.7–1.4 kg-1
the separation of succinic acid itself (Jun et al. 2007). succinic acid). This challenging objective can only be
In general, ion-exchange may be only applied as fulfilled with high-volume production plants (econ-
an additional purification step for succinic acid omy of scale) and if (i) inexpensive cellulosic raw
recovery, because selectivity is not high enough and materials can be applied as carbon source, (ii) a molar
yields remain low (Pai et al. 2002). succinic acid yield based on carbon source of more
than 1 can be achieved during fermentation (additional
fixation of CO2) with a mimimum of byproduct
Conclusions formation (organic acids) and (iii) the high down-
stream processing yields reported so far on a labora-
There have been a lot of investigations and efforts on tory scale will be realised on an industrial scale, with
designing an adequate downstream process for the the consequential lower processing costs.
recovery of succinic acid from fermentation broth. As an alternative to the complex and difficult
Most of these approaches are principally functional, isolation and purification of succinic acid from
but industrial realisation will depend on scalability, fermentation broth, Delhomme et al. (2009) reviewed
robustness, overall separation yield and costs. the catalytic possibilities of using succinic acid as a
Most of the so far proposed process schemes for C4 building block in aqueous fermentation media.
the separation of succinic acid from fermentation They came to the conclusion that the efforts and costs
broth do not result in high selectivity with respect to for purification of succinic acid from fermentation
other carboxylic acids which may be present in the broth may be reduced in the near future, if more
fermentation broth. As the final purification accounts water-stable and highly active catalysts (metal con-
for a significant cost factor, the production of these taining ones or organo-metallic complexes) become

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available for the selective and direct aqueous hydro- Hong SH, Lee SY (2001) Metabolic flux analysis for succinic
genation of succinic acid. acid production by recombinant Escherichia coli with
amplified malic enzyme activity. Biotechnol Bioeng
74:89–95
Acknowledgments This work was generously supported by Hong YK, Hong WH, Han DH (2001) Application of reactive
the Deutsche Bundesstiftung Umwelt (DBU), particularly by a extraction to recovery of carboxylic acids. Biotechnol
DBU Ph.D. grant for Tanja Kurzrock. Bioproc Eng 6:386–394
Hong YK, Han DH, Hong WH (2002) Water enhanced solu-
bilities of succinic acid in reactive extraction using tertiary
amines/alcohol systems. Korean J Chem Eng 19:83–86
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