Format

Send to

Choose Destination
J Biosci Bioeng. 2017 Nov;124(5):498-505. doi: 10.1016/j.jbiosc.2017.05.015. Epub 2017 Jun 29.

Orthogonal partial least squares/projections to latent structures regression-based metabolomics approach for identification of gene targets for improvement of 1-butanol production in Escherichia coli.

Author information

1
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: katsuaki_nitta@bio.eng.osaka-u.ac.jp.
2
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: walter_lavina@bio.eng.osaka-u.ac.jp.
3
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA 90095, USA. Electronic address: sppontrelli@gmail.com.
4
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA 90095, USA. Electronic address: liaoj@ucla.edu.
5
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: sastia_putri@bio.eng.osaka-u.ac.jp.
6
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: fukusaki@bio.eng.osaka-u.ac.jp.

Abstract

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 Escherichia coli 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.

KEYWORDS:

1-Butanol; Acetyl-CoA; CoA limitation; Escherichia coli; Metabolomics; Orthogonal partial least squares/projections to latent structures regression model; Productivity improvement

PMID:
28669528
DOI:
10.1016/j.jbiosc.2017.05.015
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center