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Springer-Verlag 1999
MINI-REVIEW
Received: 27 October 1998 / Received revision: 22 January 1999 / Accepted: 22 January 1999
Introduction
Succinic acid is a common metabolite formed by plants,
animals and microogranisms. Many anaerobic microbes
produce succinate as the major end-product of their
energy metabolism. Nonetheless, only recently has interest focused on the development of succinic acid as an
important industrial fermentation process. This review
will explain why succinic acid fermentations may, in the
future, involve larger production volumes than citric
acid, and could, perhaps, approach that of ethanol.
Green technology is becoming more of a driving force
in the chemical industry because of the current need to
decrease pollution caused by petrochemical processing
and the future need to replace the dwindling hydrocarbon economy with a renewable, environmentally sound,
carbohydrate economy.
Succinic acid as a fermentation product and process
has distinct advantages over ethanol fermentation. For
example, 2 mol waste CO2 is formed/mol glucose during
ethanol fermentation, whereas the succinate fermentation consumes CO2. Being a CO2-xing fermentation
makes succinate a very green technology. Furthermore,
integrating the succinate and ethanol fermentations with
recovery would decrease carbon lost as waste CO2 and
produce three commercial products: succinic acid, ethanol and diethyl succinate.
The industrial potential for succinic acid fermentations was recognized as early as 1980 (Zeikus 1980).
Recently, interest in higher-value organic acid fermentations, including succinic acid, has intensied especially
in the question of how it relates to utilization of agricultural carbohydrates such as corn, cassava and sugar
cane (Jain et al. 1989; Zeikus et al. 1995). The purpose
of the present review is to provide an updated view on
the potential for succinate acid fermentation and the
current achievements and limitations of the process.
546
acid sold in the food market is produced by fermentation. New fermentation technology developed at MBI
International, however, can produce succinic acid for
sale at about $ 2.20/kg at the level of 5000 tonnes/year
and the price drops to below $ 0.55/kg at above 75 000
tonnes/year. These economics promise to open new
specialty and commodity chemical markets for succinic
acid.
There are four major existing markets for succinic
acid. The rst and largest is as a surfactant/detergent
extender/foaming agent. The second market is as an ion
chelator, where it is used in electroplating to prevent
corrosion and pitting of metals. The third is the food
market, where it is used as an acidulant/pH modier, as
a avoring agent, and as an anti-microbial agent. The
fourth market is the production of health-related agents,
including pharmaceuticals, antibiotics, amino acids, and
vitamins. The total market size for these four existing
uses of succinic acid is more than $ 400 000 000/year.
Fermentation-derived succinic acid has the potential
to become a large-volume commodity chemical that
would form the basis for supplying many important
intermediate and specialty chemicals for the consumer
products industries. As a commodity chemical, succinic
acid could replace many commodities based on benzene
and intermediate petrochemicals, resulting in a large
reduction in pollution from the manufacturer and in the
consumption of over 250 benzene-derived chemicals
(Ahmed and Morris 1994). Figure 1 illustrates a potential map of the routes leading to succinic-acid-based
intermediate and specialty chemicals. The production of
succinic acid and most of its derivatives is currently at
Commodity Chemicals
Adipic Acid
Solvents
Specialty Chemicals
Polyester
1,4-Butanediol
4,4 Esters
Plant Growth
Stimulants
Tetrahydrofuran
Food Ingredients
Feed Additives
Dimethyl/Diethyl
Succinate
Gammabutyrolactone
Green Solvents
Succinic
Acid
2-Pyrrolidione
4-Amino
Butanoic Acid
Detergents and
Surfactants
Maleimide
Succinimide
Health Agents
Maleic Anhydride
Hydroxysuccinimide
Chelators and
Corrosion Inhibitors
Maleic Acid
Malic Acid
Fumaric Acid
Itaconic Acid
Aspartic Acid
547
548
Table 1 Physiological dierences between high-yielding succinate-producing bacterial strains. PEP phosphoenolpyruvate
Organism
O2 relation
Succinate pathway
Facultative
Obligate anaerobe
Mixed
PEP carboxykinase
45
65
Facultative
PEP carboxykinase
110
importantly, A. succinogenes, unlike E. coli or A. succiniciproducens, is a moderate osmophile and has high
tolerance to succinate salts, which is crucial to process
requirements for product recovery (see next section).
A. succinogenes variant strains can yield 110 g/l succinic
acid (Guettler et al. 1996). It should be pointed out that
industrial strains of Corynebacterium can make monosodium glutamate at 150 g/l. Thus 15% succinate is a
potential target product yield for future genetic strain
improvements.
A. succinogenes forms succinate via the PEP carboxykinase pathway (see Fig. 2), using four key enzymes, i.e., PEP carboxykinase, malate dehydrogenase,
fumarase, and fumarate dehydrogenase, whereas, in
E. coli, six pathways have been recognized in the formation of succinic acid, and the PEP carboxykinase
pathway plays a minor role (Clark 1989; Van der Werf
Fig. 2 Proposed catabolic
pathway for glucose fermentation in A. succiniciproducens
and A. succinogenes. Steps: 1
phosphoenolpyruvate carboxykinase, 2 malate dehydrogenase, 3 fumarate reductase, 4
pyruvate kinase, 5 pyruvate
ferredoxin oxidoreductase, 6
acetate kinase, 7 alcohol dehydrogenase, 8 lactate dehydrogenase (Samuelov et al. 1991)
Glyceraldehyde-3-phosphate
NAD
NADH
ADP
ATP
ADP
ATP
(1)
Oxaloacetate
NADH
(2)
NAD
Malate
Fumarate
ATP
XH
ADP
X
(3)
Succinate
High CO2
CO2
ATP
(4)
NAD
NADH
Pyruvate
CoA
CO2 (5)
X
XH
Acetyl CoA
(8)
Lactate
Formate
NADH
NAD
Acetyl phosphate
ADP
(6)
ATP
Acetaldehyde
NADH
NAD
(7)
Ethanol
Acetate
Low CO2
549
550
Steam
NaOH
Makeup
F-1
Wash
Sterilizer
Inoculation
Train
F-2
Spent Cells
F-3
Cooling Water
Production
Fermentors
Condensate
Succinic
Acid
Base Recycle
CO2
Broth
Harvest
Tank
Microporous
Filter
ED Concentrate Succinate
Electrolytes
& CIP Fluids
Regenerant
Succinic
Acid Crystals
Spent Broth
50% Succinic
Acid Solution
Crystallizer Mother Liquor Recycle
Bipolar
Electrodialysis
Sodium
Succinate
Chelating Ion
Exchange Columns
Spent Broth
ED Electrolytes
& CIP Fluids
Desalting
Electrodialzer
551
)
noted that the commodity price for glucose is approximately $ 0.18/kg and, because more than 1 kg succinic
acid is produced/kg glucose, a future target production
price of $ 0.35/kg succinic acid seems reasonable.
The theoretical chemical yield for succinic acid is:
C6 H12 O6 CO2 ! 1 HCOOCACH2 ACH2 ACOOH
1 CH3 COOH HCOOH
Theoretical chemical yield improvements can also be
made with strains that consume H2 or HCOOH as follows:
C6 H12 O6 2CO2 2 H2
! 2 HOOCACH2 ACH2 ACOOH 2 H2 O
C6 H12 O6 2 HCOOH
! 2 HOOCACH2 ACH2 ACOOH 2 H2 O
These theoretical succinate yields have not yet been
achieved in practice. We are currently demonstrating, in
electrochemical bioreactor systems using electron mediators, that H2 can be replaced by electricity as an electron donor for enhanced succinate production (Park
DH, Laivenieks M, Guettler MV, Jain MK, Zeikus JG,
unpublished data). During fermentation by Actinobacillus on glucose plus electricity, electricity was found to
enhance glucose consumption, growth and succinate
production by approximately 25%, while it decreased
acetate production by approximately 50%. Genetic
engineering techniques now need to be used on
A. succinogenes strains to achieve the theoretical
succinate yield of two moles of succinate from one glucose and two CO2.
Similarly, there is still the considerable task of lowering the costs of succinic acid recovery technology.
Decreasing the number of unit operations and developing lower-cost liquid-extraction procedures appear to
be promising ways of improving the overall process
economics.
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Corn
Starch/Glucose
CO2
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