초록
<P>Metabolomics is the comprehensive analysis of metabolites in biological systems that uses multivariate analyses such as principal component analysis (PCA) or partial least squares/projections to latent structures regression (PLSR) to understand the metabolome state and extract important information from biological systems. In this study, orthogonal PLSR (OPLSR) model-based metabolomics approach was applied to 1-butanol producing <I>Escherichia coli</I> to facilitate in strain improvement strategies. Here, metabolite data obtained by liquid chromatography/mass spectrometry (LC/MS) was used to construct an OPLSR model to correlate metabolite changes with 1-butanol production and rationally identify gene targets for strain improvement. Using this approach, acetyl-CoA was determined as the rate-limiting step of the pathway while free CoA was found to be insufficient for 1-butanol production. By resolving the problems addressed by the OPLSR model, higher 1-butanol productivity was achieved. In this study, the usefulness of OPLSR-based metabolomics approach for understanding the whole metabolome state and determining the most relevant metabolites was demonstrated. Moreover, it was able to provide valuable insights for selection of rational gene targets for strain improvement.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This paper is the first report of an OPLSR-based metabolomics approach for strain improvement of 1-butanol producing <I>E.coli.</I> </LI> <LI> Resolving acetyl-CoA to acetoacetyl-CoA bottleneck reaction improved 1-butanol productivity in the highest producing strain. </LI> <LI> OPLSR-based metabolomics approach also indicated a CoA limitation in the highest producing strain. </LI> </UL> </P>