Mutations Elevate an Underground Pathway to a Physiologically Relevant Protopathway.

ABSTRACT: Underground metabolic pathways-leaks in the metabolic network caused by promiscuous enzyme activities and nonenzymatic transformations-can provide the starting point for emergence of novel protopathways if a mutation or environmental change increases flux to a physiologically significant level. This early stage in pathway evolution, in which promiscuous enzymes are still serving their native functions and proper regulation has not yet emerged, is typically hidden from our view. We previously used laboratory evolution to evolve a novel four-step protopathway in ΔpdxB E. coli, which lacks an enzyme required for synthesis of pyridoxal 5'-phosphate (PLP). By sequencing population genomic DNA from samples archived during the evolution experiment, we have identified mutations that rose and fell

SUBMITTER: Widney KA 

PROVIDER: S-EPMC12393044 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature