Biomedical Engineering Reference
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maleic acid (or maleic anhydride), obtained from benzene oxidation [ 125 ].
However, fumaric acid can also be accumulated by microorganisms, particularly
those belonging to the genus Rhizopus. Fumaric acid production by fermentation was
operated in the USA as early as the 1940s, but later this process was discontinued and
replaced by chemical synthesis due to its low productivity and the cheap availability
of petroleum-derived feedstock. However, today, people are more concerned about
natural products, especially in the food and pharmaceutical industry, and thus
fermentative fumaric acid production is urgently needed [ 106 , 126 ].
The economics of the fermentation route is still less favorable than the petro-
chemical route, in particular the raw material costs. Many studies have been con-
ducted on the potential of utilizing cheap raw materials, such as lignocellulose
resources. Liao et al. [ 127 ] developed a three-step fermentation process for fumaric
acid production by R. oryzae from animal manure hydrolyzate, which was rich in
glucose and xylose; under optimal conditions, a fumaric acid yield of 31%, and a
chitin content of 0.21 g/g biomass was reached. Fumaric acid can also be produced
from pure xylose. Kautola and Linko [ 128 ] used immobilized Rhizopus arrhizus to
ferment xylose; when the initial xylose concentration was 100 g/L, a fumaric acid
productivity of 0.087 g/(L h) was obtained. Fumaric acid production using
hemicellulose hydrolyzate directly as substrate has also been studied. Woicie-
chowski et al. [ 129 ] investigated the performance of different strains in fumaric acid
production with wood chips hydrolyzate as substrate; two R. arrhizus strains showed
the highest amount of fumaric acid accumulation: 5.085 g/L of fumaric acid could be
generated from 56.55 g/L sugar. However, the utilization rate of the hemicellulose-
derived sugars, especially pentose, are rather slow compared with using glucose as
substrate. To overcome this obstacle, a novel strategy to utilize hemicellulose-
derived sugars was developed during fumaric acid production from lignocellulose.
Liu et al. [ 130 ] observed that xylose was more suitable for R. arrhizus to accumulate
biomass than glucose. Tai et al. [ 131 ] further observed that hemicellulose was an
excellent substrate for the growth of fumaric acid-producing fungus, and that
chitosan accumulated on the cell membrane. Depending on the pretreatment meth-
ods, sugars contained in the hemicellulosic fraction could be separated from the
cellulose fraction. A two-stage corn straw utilization strategy for fumaric acid pro-
duction was thus developed by Xu et al. [ 132 ] (Fig. 5 ). Corn straw was first pretreated
by dilute sulphuric acid to obtain a xylose-rich liquid (hemicellulose hydrolyzate)
that could be used as a carbon source to increase fungal biomass and chitosan
accumulation; in addition the residue of corn straw was digested by enzyme to obtain
a glucose-rich liquid that could be used for fumaric acid production. Under optimal
conditions, fumaric acid production was up to 27.79 g/g, with yield of 0.35 g/g and
productivity of 0.33 g/(L h).
Succinic acid is another organic acid that could be generated from hemicel-
lulose sugars. It is a valuable four-carbon intermediate that can be used as the
precursor of many important industrial chemicals: 1,4-butanediol, tetrahydrofuran,
N-methyl pyrrolidinone, 2-pyrrolidinone, and several others. Furthermore, the
demand for succinic acid extends to the synthesis of biodegradable polymers such
as polybutyrate succinate (PBS) and polyamides [ 133 ]. Currently, succinic acid is
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