A dynamic pathway analysis approach reveals a limiting futile cycle in N-acetylglucosamine overproducing Bacillus subtilis.

ABSTRACT: Recent advances in genome engineering have further widened the gap between our ability to implement essentially any genetic change and understanding the impact of these changes on cellular function. We lack efficient methods to diagnose limiting steps in engineered pathways. Here, we develop a generally applicable approach to reveal limiting steps within a synthetic pathway. It is based on monitoring metabolite dynamics and simplified kinetic modelling to differentiate between putative causes of limiting product synthesis during the start-up phase of the pathway with near-maximal rates. We examine the synthetic N-acetylglucosamine (GlcNAc) pathway in Bacillus subtilis and find none of the acetyl-, amine- or glucose-moiety precursors to limit synthesis. Our dynamic metabolomics approach pre

SUBMITTER: Liu Y 

PROVIDER: S-EPMC5512609 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature