Energy, industries (e.g., solvents (1,4-butanediol, tetra-hydrofuran, 2-pyrrolidinone, and

Energy, or simply ATP, is the ultimate
reason for all the metabolisms in all living cells. Microorganisms can gain
energy by processes such as aerobic/anaerobic respiration, fermentation and
photosynthesis. This process is mostly accompanied by other metabolisms such as
chemotaxis, nutrient uptake, secretion of polymers, efflux of waste metabolites
and toxic compounds. These metabolic routes in some cases are the desired
bioprocesses to produce high-value chemicals, such as organic acids (Ward, 2015).

Succinic acid (SA) also known as amber
acid was first obtained by dry distillation of amber (succinum) in 1550s (Kamm
et al., 2008). Currently succinic acid can be produced either via petrochemical
or from bio- processes. Succinic acid is the term used for SA produced by petrochemical
processes, while the SA produced through biotechnological processes with
renewable substrate is referred to as bio-succinic acid (bioSA). The prevailing
production of bio-succinic acid is through fermentation, which has the
important feature of consuming carbon (one mol of CO2 is consumed
per mol of succinic acid produced), and this can be considered an environmental
advantage over the petrochemical derived equivalent.

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Succinic acid is a precursor in the
chemical synthesis of numerous commodities in agricultural, food, chemical and
pharmaceutical industries (e.g., solvents (1,4-butanediol, tetra-hydrofuran,
2-pyrrolidinone, and gamma-butyrolactone) and biodegradable polymers
(polybutylene succinate (PBS) and polyamides)) (Bechthold et al., 2008; Ingólfur B. Gunnarsson et
al., 2014).  Succinic acid has a wide
range of industrial applications, such as chemical intermediate for the
production of lacquers and perfume esters as well as a flavor, bacteriostatic,
or neutralizing agent in the food industry. Furthermore, succinic acid also has
a special chemical market for producing coatings, surfactants, dyes,
detergents, green solvents, biodegradable plastics, and ingredients stimulating
animal (K.-K. Cheng et al., 2012). In 2004, succinic acid was identified
by the U.S. Department of Energy as one of the top 12 value added
biomass-derived compounds with the potential to replace a large number of
intermediates and specialty chemicals derived from benzene or other petrochemicals
(Werpy et al., 2004).
Particularly, it is seen as a bio- replacement for maleic acid in a number of
applications due to its similar chemical properties (Cukalovic and Stevens, 2008).
Despite its uses in agricultural, food and pharmaceutical industry (Zeikus et al., 1999),
succinic acid has been considered a niche product and never a relevant
intermediate in the chemical industry, mainly due to its high price (Bechthold et al., 2008; Taylor, 2010).

Rising atmospheric greenhouse gas
concentrations, increasing oil prices, security of supply, and the need to
build a sustainable global economy are all strong incentives for the transition
from fossil-fuel based succinic acid production toward bio-based alternative (Bechthold et al., 2008; Sauer et al., 2008). To
this respect, numerous companies and research institutes are currently
developing and optimizing bio-succinic acid production routes (Daedal, 2014). In 1999,
the worldwide succinic acid production was estimated to be 15,000 MT (being
mostly petro-based derived) (Zeikus et al., 1999) while
it increased to approximately 30,000 – 50,000 MT in 2011 (Cheng et al., 2012; Daedal, 2014; Pinazo et al.,
Currently, bio- succinic acid is produced by mainly four companies; BioAmber,
Reverdia, Succinity which is a joint venture between BASF and Purac, and Myriant
(Weastra, 2012). As
of 2016, BioAmber (Sarnia Ontario, Canada) was the largest producer of bio-
succinic acid worldwide, with a capacity of 30,000 MTPA, followed by Myriant
(Lake Providence Louisiana, USA) with a capacity of 14,000 MTPA and then
Reverdia (Cassano Spinola, Italy) and Succinity (Barcelona, Spain) with a
capacity of 10,000 MTPA each1. In addition to the
extensive research work made by numerous research institutes, these companies
have developed and patented technological processes to make bio-succinic acid
competitive with its petrochemical alternative.

the importance of the biotechnological production of succinic acid, an overview
of petrochemical and bio-based succinic acid production routes are provided in
sections ?2.1-?2.2, with more detailed metabolic route of
fermentation route (as the most predominant bio-based route for SA production)
in section ?2.2.1. However, the limitations of anaerobic process
have made a new trend in SA production which is the alternative aerobic or dual
phase processes (described in sections ?2.2.2 and ?2.2.3). Besides strain improvement, optimization of
process parameters such as substrate type, pH and carbonate source, operational
mode and reactor configuration are also important factors in achieving high
titer, yield and production rate, the overview of which are provided
exclusively in sections ?3.1?- 3.3. However, as the main goal of SA production is
to reduce production and separation costs for the SA production bioprocess in
order to become competitive with petrochemical production route from maleic
acid (Patel, 2006), downstream processing is also a critical point
in SA production. The key challenge to successful separation of succinic acid
from fermentation broth is how to apply this technology to large-scale
industrial processes in a cost-and time-effective manner leading to cheaper SA
product. Therefore, the conventional and alternative efficient techniques for
SA recovery and separation are studied at the final section of ?4, with a discussion on advantages and
disadvantages of each technique.


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