92
commercial- scale IA production [19]. Most IA production (about 76%) facilities
are located in China [20]. After China, Alpha Chemika (India) and Itaconix Co.
(USA) are the major IA producers [21].
As a result of the EU restriction on the use of sodium tri(poly)phosphate to prevent eutrophication in the industrial production of detergents, polyitaconic acid (a
derivative of IA) was used instead. In 2015, Germany was the leading producer of
IA in the EU with market size of $2.8 million [22].
2.2 Bio-Catalytic Pathway for the Production of IA
IA is exclusively produced by submerged batch culture process using a highproducing strain of A. terreus [23, 24]. In this process high sugar (glucose or
sucrose) concentration and continuous supply of high amounts of oxygen are
needed, which make the process expensive. Another drawback is that the growth of
A. terreus fungus is sensitive to phosphate impurities [25, 26]. The following sections described the use of different fungi, yeasts, and bacteria for IA biosynthesis.
2.2.1 IA Production by Fungi
Ustilago maydis Ustilago maydis (U. maydis) is a biotrophic organism that can be
utilized for the synthesis of IA [27]. Advantages such as unicellular growth pattern,
lower sensitivity to impurities, homogenous oxygenation, and easy genetic manipulation make this fungus a possible alternative to A. terreus. The production process
of IA by both of these fungi is different. Using Ustilago and related species, IA is
produced at pH above 5, whereas comparatively low pH is required in the case of
A. terreus. In addition, IA production by most Ustilago species is triggered under
nitrogen-limited environment, whereas phosphate limitation applies to A. terreus.
U. maydis follows an uncommon metabolic pathway different from the reported
pathway of A. terreus (Fig. 2) [28]. Despite the very different lifestyles of these
fungi, the function of transporters involved in the synthesis of IA is likely similar in
both cases [29]. The activities of such transporters are significantly affected by
either amino acid sequence or primary structure of the protein and underlying biosynthetic pathways. Wierckx et al. showed that the mitochondrial tricarboxylate
transporter from A. terreus (At_MttA) allows greater itaconate yield in U. maydis
than overexpressing the natural mitochondrial tricarboxylate transporter (mtt1) [30].
Most U. maydis-catalyzed fermentation reaction was performed on a lab scale in
shake flasks. Guevarra and Tabuchi synthesized various carboxylic acids with the
aid of this fungus with IA yield of 53 g L
−1
[31]. Klement et al. reported the production of IA from glucose using U. maydis wild-type strain MB215 under nitrogenrestricted conditions, and the optimum IA concentration achieved was 20 g L
−1
[32].
Nitrogen limitation is crucial for the effective production of IA. The main problem
K. Avasthi et al.
commercial- scale IA production [19]. Most IA production (about 76%) facilities
are located in China [20]. After China, Alpha Chemika (India) and Itaconix Co.
(USA) are the major IA producers [21].
As a result of the EU restriction on the use of sodium tri(poly)phosphate to prevent eutrophication in the industrial production of detergents, polyitaconic acid (a
derivative of IA) was used instead. In 2015, Germany was the leading producer of
IA in the EU with market size of $2.8 million [22].
2.2 Bio-Catalytic Pathway for the Production of IA
IA is exclusively produced by submerged batch culture process using a highproducing strain of A. terreus [23, 24]. In this process high sugar (glucose or
sucrose) concentration and continuous supply of high amounts of oxygen are
needed, which make the process expensive. Another drawback is that the growth of
A. terreus fungus is sensitive to phosphate impurities [25, 26]. The following sections described the use of different fungi, yeasts, and bacteria for IA biosynthesis.
2.2.1 IA Production by Fungi
Ustilago maydis Ustilago maydis (U. maydis) is a biotrophic organism that can be
utilized for the synthesis of IA [27]. Advantages such as unicellular growth pattern,
lower sensitivity to impurities, homogenous oxygenation, and easy genetic manipulation make this fungus a possible alternative to A. terreus. The production process
of IA by both of these fungi is different. Using Ustilago and related species, IA is
produced at pH above 5, whereas comparatively low pH is required in the case of
A. terreus. In addition, IA production by most Ustilago species is triggered under
nitrogen-limited environment, whereas phosphate limitation applies to A. terreus.
U. maydis follows an uncommon metabolic pathway different from the reported
pathway of A. terreus (Fig. 2) [28]. Despite the very different lifestyles of these
fungi, the function of transporters involved in the synthesis of IA is likely similar in
both cases [29]. The activities of such transporters are significantly affected by
either amino acid sequence or primary structure of the protein and underlying biosynthetic pathways. Wierckx et al. showed that the mitochondrial tricarboxylate
transporter from A. terreus (At_MttA) allows greater itaconate yield in U. maydis
than overexpressing the natural mitochondrial tricarboxylate transporter (mtt1) [30].
Most U. maydis-catalyzed fermentation reaction was performed on a lab scale in
shake flasks. Guevarra and Tabuchi synthesized various carboxylic acids with the
aid of this fungus with IA yield of 53 g L
−1
[31]. Klement et al. reported the production of IA from glucose using U. maydis wild-type strain MB215 under nitrogenrestricted conditions, and the optimum IA concentration achieved was 20 g L
−1
[32].
Nitrogen limitation is crucial for the effective production of IA. The main problem
K. Avasthi et al.