AibA/AibB Induces an Intramolecular Decarboxylation in Isovalerate Biosynthesis by Myxococcus xanthus. Issue 33 (16th May 2017)

• Record Type: Journal Article
• Authors: Bock, Tobias; Luxenburger, Eva; Hoffmann, Judith; Schütza, Vlad; Feiler, Christian; Müller, Rolf; Blankenfeldt, Wulf
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 33(2017)
• Page Start: 9986
• Page End: 9989
• Publication Date: 2017-05-16
• Subjects: biosynthesis -- decarboxylation -- enzymes -- protein expression -- structural biology; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201701992
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : Based on structural and biochemical characterization of the unique cofactor‐free decarboxylase AibA/AibB, an intramolecular decarboxylation mechanism supported by the geometry and hydrophobic character of the active site is proposed. This study opens up opportunities for synthetic biology approaches, since AibA/AibB is well‐suited to the bacterial production of isobutene, a precursor of renewable biofuels and chemicals.