This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: 2-methylsuccinate degradation
|Superclasses:||Degradation/Utilization/Assimilation → Carboxylates Degradation|
itaconate is an unsaturated acid with conjugated double bonds and two carboxyl groups. The acid was discovered in 1837 [Baup37], and was named itaconate as an anagram of cis-aconitate, from which it was first derived by Crasso in 1840 [Turner41].
Because of its unique structure and characteristics, itaconate and its ester are useful materials for the bioindustry. It is used for the synthesis of fiber, resin, plastic, rubber, paints, surfactant, ion-exchange resins and lubricant [Dwiarti07].
Many microorganisms are able to grow on itaconate as their sole source of carbon [Nagai63, Brightman61]. In addition, itaconate is oxidized in liver mitochondria in a pathway that involves activation to itaconyl-CoA followed by hydration and cleavage to yield acetyl-CoA and pyruvate [Adler57, Wang61].
Pseudomonas sp. B2aba was shown to employ a pathway that is very similar to that found in liver mitochondria [Cooper64]. When cell-free extracts were incubated with itaconate, Mg2+, ions, coenzyme A and ATP, pyruvate was formed. The amount of pyruvate formed was proportional to the quantities of coenzyme A added. Synthetic itaconyl-CoA could replace itaconate , coenzyme A and ATP, suggesting that itaconate is first activated to itaconyl-CoA.
In addition, washed suspensions of Pseudomonas sp. B2aba grown on itaconate readily oxidized (S)-citramalate, whereas washed suspensions of the organism grown on succinate did not. Further studies established that in the presence of succinyl-CoA and itaconate (3S)-citramalyl-CoA is formed as an intermediate in the pathway. A similar conculsion was arrived in an earlier study with Pseudomonas fluorescens [Nagai63].
The three enzymes succinyl-CoA:itaconate CoA transferase, itaconyl-CoA hydratase and citramalyl-CoA lyase were partially purifed, and shown to catalyze the conversion of itaconate to pyruvate and acetyl-CoA in vitro. The first enzyme was also able to accept (S)-citramalate as substrate, enabling the organism to grow on (S)-citramalate. All of these enzymes were induced by growth on itaconate, (S)-citramalate or methylsuccinate.
A fourth enzyme, itaconyl-CoA synthetase, was isolated and shown to form itaconyl-CoA from itaconate. This enzyme was shown to be identical to (GDP-forming) succinyl-CoA synthetase, and was not inducible [Cooper64].
Dwiarti07: Dwiarti L, Otsuka M, Miura S, Yaguchi M, Okabe M (2007). "Itaconic acid production using sago starch hydrolysate by Aspergillus terreus TN484-M1." Bioresour Technol 98(17);3329-37. PMID: 17451943
Dimroth77a: Dimroth P, Buckel W, Loyal R, Eggerer H (1977). "Isolation and function of the subunits of citramalate lyase and formation of hybrids with the subunits of citrate lyase." Eur J Biochem 1977;80(2);469-77. PMID: 923590
Michelucci13: Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A, Buttini M, Linster CL, Medina E, Balling R, Hiller K (2013). "Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production." Proc Natl Acad Sci U S A 110(19);7820-5. PMID: 23610393
Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216
Zarzycki09: Zarzycki J, Brecht V, Muller M, Fuchs G (2009). "Identifying the missing steps of the autotrophic 3-hydroxypropionate CO2 fixation cycle in Chloroflexus aurantiacus." Proc Natl Acad Sci U S A 106(50);21317-22. PMID: 19955419
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