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Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients.

ABSTRACT: Maintenance of bacterial cell shape and resistance to osmotic stress by the peptidoglycan (PG) renders PG biosynthetic enzymes and precursors attractive targets for combating bacterial infections. Here, by applying native mass spectrometry, we elucidate the effects of lipid substrates on the PG membrane enzymes MraY, MurG, and MurJ. We show that dimerization of MraY is coupled with binding of the carrier lipid substrate undecaprenyl phosphate (C₅₅-P). Further, we demonstrate the use of native MS for biosynthetic reaction monitoring and find that the passage of substrates and products is controlled by the relative binding affinities of the different membrane enzymes. Overall, we provide a molecular view of how PG membrane enzymes convey lipid precursors through favourable binding events and highlight possible opportunities for intervention.

SUBMITTER: Oluwole AO

PROVIDER: S-EPMC9046198 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients.

Oluwole Abraham O AO Corey Robin A RA Brown Chelsea M CM Hernández-Rocamora Victor M VM Stansfeld Phillip J PJ Vollmer Waldemar W Bolla Jani R JR Robinson Carol V CV

Nature communications 20220427 1

Maintenance of bacterial cell shape and resistance to osmotic stress by the peptidoglycan (PG) renders PG biosynthetic enzymes and precursors attractive targets for combating bacterial infections. Here, by applying native mass spectrometry, we elucidate the effects of lipid substrates on the PG membrane enzymes MraY, MurG, and MurJ. We show that dimerization of MraY is coupled with binding of the carrier lipid substrate undecaprenyl phosphate (C<sub>55</sub>-P). Further, we demonstrate the use o ...[more]

PMID: 35477938

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