Cellular and Structural Basis of Synthesis of the Unique Intermediate Dehydro-F₄₂₀-0 in Mycobacteria.

ABSTRACT: F₄₂₀ is a low-potential redox cofactor used by diverse bacteria and archaea. In mycobacteria, this cofactor has multiple roles, including adaptation to redox stress, cell wall biosynthesis, and activation of the clinical antitubercular prodrugs pretomanid and delamanid. A recent biochemical study proposed a revised biosynthesis pathway for F₄₂₀ in mycobacteria; it was suggested that phosphoenolpyruvate served as a metabolic precursor for this pathway, rather than 2-phospholactate as long proposed, but these findings were subsequently challenged. In this work, we combined metabolomic, genetic, and structural analyses to resolve these discrepancies and determine the basis of F₄₂₀ biosynthesis in mycobacterial cells. We show that, in whole cells of Mycobact

SUBMITTER: Grinter R 

PROVIDER: S-EPMC7253369 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature