Ein alternativer Isovaleryl‐CoA‐Biosyntheseweg: Beteiligung einer bisher unbekannten 3‐Methylglutaconyl‐CoA‐Decarboxylase

Isovaleryl-Coenzym A( IV-CoA) ist eine wichtige Vorstufe fürI sofettsäuren und Lipide,d ie in Myxobakterien essentiell fürdie Entwicklung sind. Myxobakterien kçnnen IV-CoA aus Acetyl-CoA über eine alternative IV-CoA-Biosynthese (aib) herstellen. Die zentrale Reaktion in aib wird durch die kofaktorfreie Decarboxylase AibA/AibB katalysiert. Wir entwickelten ein effizientes Expressionssystem fürAibA/AibB, das die Bestimmung hochaufgelçster Kristallstrukturen im Komplex mit verschiedenen Liganden ermçglichte.D urch Mutation zeigen wir,d ass ein Cystein, das als katalytisch wichtig beschrieben wurde, fürdie enzymatischeAktivitätnicht bençtigt wird. Stattdessen scheint AibA/AibB eine intramolekulare Decarboxylierung zu induzieren, indem es das Substrat in eine gebogene Konformation in der hydrophoben Tasche zwingt. Da AibA/AibB in der Produktion von Isobuten, einem Vorläufer fürB iotreibstoff,e ingesetzt werden kçnnte,e rçffnet unsere Arbeit neue Wege in der synthetischen Biologie.

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AibA/AibB induziert eine intramolekulare Decarboxylierung in der De‐novo‐Biosynthese von Isovalerat aus Myxococcus xanthus

Böck

Luxenburger

Hoffmann

et al. 2017

Angewandte Chemie

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Mechanism of 3‐Methylglutaconyl CoA Decarboxylase AibA/AibB: Pericyclic Reaction versus Direct Decarboxylation

Sheng

Himo

2020

Angewandte Chemie

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The enzyme 3-methylglutaconyl coenzyme A (CoA) decarboxylase (called AibA/AibB) catalyzes the decarboxylation of 3-methylglutaconyl CoA to generate 3,3-dimethylacrylyl-CoA, representing an important step in the biosynthesis of isovaleryl-coenzyme A in Myxococcus xanthus when the regular pathway is blocked. A novel mechanism involving a pericyclic transition state has previously been proposed for this enzyme, making AibA/AibB unique among decarboxylases. Herein, density functional calculations are used to examine the energetic feasibility of this mechanism. It is shown that the intramolecular pericyclic reaction is associated with a very high energy barrier that is similar to the barrier of the same reaction in the absence of the enzyme. Instead, the calculations show that a direct decarboxylation mechanism has feasible energy barriers that are in line with the experimental observations.

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AibA/AibB Induces an Intramolecular Decarboxylation in Isovalerate Biosynthesis by Myxococcus xanthus

et al. 2017

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Isovaleryl coenzyme A (IV-CoA) is an important precursor for iso-fatty acids and lipids. It acts in the development of myxobacteria, which can produce this compound from acetyl-CoA through alternative IV-CoA biosynthesis (aib). A central reaction of aib is catalyzed by AibA/AibB, which acts as a cofactor-free decarboxylase despite belonging to the family of CoA-transferases. We developed an efficient expression system for AibA/AibB that allowed the determination of high-resolution crystal structures in complex with different ligands. Through mutational studies, we show that an active-site cysteine previously proposed to be involved in decarboxylation is not required for activity. Instead, AibA/AibB seems to induce an intramolecular decarboxylation by binding its substrate in a hydrophobic cavity and forcing it into a bent conformation. Our study opens opportunities for synthetic biology studies, since AibA/AibB may be suitable for the production of isobutene, a precursor of biofuels and chemicals.

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Ein alternativer Isovaleryl‐CoA‐Biosyntheseweg: Beteiligung einer bisher unbekannten 3‐Methylglutaconyl‐CoA‐Decarboxylase

Cited by 7 publications

References 28 publications

AibA/AibB induziert eine intramolekulare Decarboxylierung in der De‐novo‐Biosynthese von Isovalerat aus Myxococcus xanthus

AibA/AibB induziert eine intramolekulare Decarboxylierung in der De‐novo‐Biosynthese von Isovalerat aus Myxococcus xanthus

Mechanism of 3‐Methylglutaconyl CoA Decarboxylase AibA/AibB: Pericyclic Reaction versus Direct Decarboxylation

AibA/AibB Induces an Intramolecular Decarboxylation in Isovalerate Biosynthesis by Myxococcus xanthus

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