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. 2015 Aug 15;81(16):5632-8.
doi: 10.1128/AEM.00822-15. Epub 2015 Jun 12.

Mesaconase Activity of Class I Fumarase Contributes to Mesaconate Utilization by Burkholderia xenovorans

Miriam Kronen  1 , Jahminy Sasikaran  1 , Ivan A Berg  2
Affiliations

Mesaconase Activity of Class I Fumarase Contributes to Mesaconate Utilization by Burkholderia xenovorans

Miriam Kronen et al. Appl Environ Microbiol. .

Abstract

Pseudomonas aeruginosa, Yersinia pestis, and many other bacteria are able to utilize the C5-dicarboxylic acid itaconate (methylenesuccinate). Itaconate degradation starts with its activation to itaconyl coenzyme A (itaconyl-CoA), which is further hydrated to (S)-citramalyl-CoA, and citramalyl-CoA is finally cleaved into acetyl-CoA and pyruvate. The xenobiotic-degrading betaproteobacterium Burkholderia xenovorans possesses a P. aeruginosa-like itaconate degradation gene cluster and is able to grow on itaconate and its isomer mesaconate (methylfumarate). Although itaconate degradation proceeds in B. xenovorans in the same way as in P. aeruginosa, the pathway of mesaconate utilization is not known. Here, we show that mesaconate is metabolized through its hydration to (S)-citramalate. The latter compound is then metabolized to acetyl-CoA and pyruvate with the participation of two enzymes of the itaconate degradation pathway, a promiscuous itaconate-CoA transferase able to activate (S)-citramalate in addition to itaconate and (S)-citramalyl-CoA lyase. The first reaction of the pathway, the mesaconate hydratase (mesaconase) reaction, is catalyzed by a class I fumarase. As this enzyme (Bxe_A3136) has similar efficiencies (kcat/Km) for both fumarate and mesaconate hydration, we conclude that B. xenovorans class I fumarase is in fact a promiscuous fumarase/mesaconase. This promiscuity is physiologically relevant, as it allows the growth of this bacterium on mesaconate as a sole carbon and energy source.

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Figures

FIG 1
FIG 1
Itaconate and mesaconate metabolism in Pseudomonas aeruginosa and Burkholderia xenovorans (adapted from reference 11). Enzymes: 1, succinyl-CoA:itaconate-CoA transferase (referred to in the text as itaconate-CoA transferase); 2, itaconyl-CoA isomerase/mesaconyl-CoA hydratase (referred to in the text as itaconyl-CoA hydratase); 3, (S)-citramalyl-CoA lyase; 4, mesaconase. Note that itaconate-CoA transferase is able to catalyze both itaconate and (S)-citramalate activation (11) and that succinyl-CoA synthetase is capable of activating itaconate as well.
FIG 2
FIG 2
Gene clusters encoding enzymes of itaconate degradation in P. aeruginosa and B. xenovorans (15, 47). The cluster contains genes encoding hypothetical proteins (three in P. aeruginosa, two in B. xenovorans) as well as the following genes: ccl, for (S)-citramalyl-CoA lyase; ich, for itaconyl-CoA hydratase; ict, for succinyl-CoA:itaconate-CoA transferase. The percentage of sequence identity/similarity of the corresponding proteins to those from P. aeruginosa is shown in parentheses.
FIG 3
FIG 3
Growth of B. xenovorans on acetate (●), itaconate (■), and mesaconate (▲). The experiment was done in triplicate, with the error bars representing the standard deviations.
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