Diversification by CofC and Control by CofD Govern Biosynthesis and Evolution of Coenzyme F₄₂₀ and Its Derivative 3PG-F₄₂₀.

ABSTRACT: Coenzyme F₄₂₀ is a microbial redox cofactor that mediates diverse physiological functions and is increasingly used for biocatalytic applications. Recently, diversified biosynthetic routes to F₄₂₀ and the discovery of a derivative, 3PG-F₄₂₀, were reported. 3PG-F₄₂₀ is formed via activation of 3-phospho-d-glycerate (3-PG) by CofC, but the structural basis of substrate binding, its evolution, as well as the role of CofD in substrate selection remained elusive. Here, we present a crystal structure of the 3-PG-activating CofC from Mycetohabitans sp. B3 and define amino acids governing substrate specificity. Site-directed mutagenesis enabled bidirectional switching of specificity and thereby revealed the short evolutionary trajectory to 3PG-F

SUBMITTER: Hasan M 

PROVIDER: S-EPMC8764529 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature