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

Angewandte Chemie
Tobias BockWulf Blankenfeldt

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.

References

Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Oct 11, 2008·Chembiochem : a European Journal of Chemical Biology·Helge B BodeRolf Müller
Apr 29, 2016·Chembiochem : a European Journal of Chemical Biology·Tobias BockWulf Blankenfeldt
Aug 5, 2016·Acta Crystallographica. Section F, Structural Biology Communications·Tobias BockWulf Blankenfeldt

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Citations

Jun 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·James M ClomburgRamon Gonzalez
Sep 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Fangfang ChenFrank Pessler
Dec 3, 2020·Acta Crystallographica. Section F, Structural Biology Communications·Christian G FeilerWulf Blankenfeldt
Feb 1, 2019·International Journal of Biological Macromolecules·Débora M A CostaTiago A S Brandão

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