Conversion of anthranilate synthase into isochorismate synthase: implications for the evolution of chorismate-utilizing enzymes

Angewandte Chemie
Maximilian G PlachReinhard Sterner

Abstract

Chorismate-utilizing enzymes play a vital role in the biosynthesis of metabolites in plants as well as free-living and infectious microorganisms. Among these enzymes are the homologous primary metabolic anthranilate synthase (AS) and secondary metabolic isochorismate synthase (ICS). Both catalyze mechanistically related reactions by using ammonia and water as nucleophiles, respectively. We report that the nucleophile specificity of AS can be extended from ammonia to water by just two amino acid exchanges in a channel leading to the active site. The observed ICS/AS bifunctionality demonstrates that a secondary metabolic enzyme can readily evolve from a primary metabolic enzyme without requiring an initial gene duplication event. In a general sense, these findings add to our understanding how nature has used the structurally predetermined features of enzyme superfamilies to evolve new reactions.

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Citations

Dec 25, 2015·Fungal Genetics and Biology : FG & B·Pin-Mei WangNancy P Keller
May 27, 2017·BMC Bioinformatics·Florian KandlingerRainer Merkl
May 16, 2019·Chembiochem : a European Journal of Chemical Biology·Michael SchupfnerReinhard Sterner
Apr 24, 2018·Frontiers in Molecular Biosciences·Anutthaman ParthasarathyAndré O Hudson
Feb 20, 2021·Chemical Communications : Chem Comm·Florian HubrichJennifer N Andexer
Jun 3, 2021·Biomolecules·Awdhesh Kumar Mishra, Kwang-Hyun Baek

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