Streamlined identification of strain engineering targets for bioprocess improvement using metabolic pathway enrichment analysis

Cortada-Garcia, J., Daly, R. , Alison Arnold, S. and Burgess, K. (2023) Streamlined identification of strain engineering targets for bioprocess improvement using metabolic pathway enrichment analysis. Scientific Reports, 13, 12990. (doi: 10.1038/s41598-023-39661-x) (PMID:37563133) (PMCID:PMC10415327)

Abstract

Metabolomics is a powerful tool for the identification of genetic targets for bioprocess optimisation. However, in most cases, only the biosynthetic pathway directed to product formation is analysed, limiting the identification of these targets. Some studies have used untargeted metabolomics, allowing a more unbiased approach, but data interpretation using multivariate analysis is usually not straightforward and requires time and effort. Here we show, for the first time, the application of metabolic pathway enrichment analysis using untargeted and targeted metabolomics data to identify genetic targets for bioprocess improvement in a more streamlined way. The analysis of an Escherichia coli succinate production bioprocess with this methodology revealed three significantly modulated pathways during the product formation phase: the pentose phosphate pathway, pantothenate and CoA biosynthesis and ascorbate and aldarate metabolism. From these, the two former pathways are consistent with previous efforts to improve succinate production in Escherichia coli. Furthermore, to the best of our knowledge, ascorbate and aldarate metabolism is a newly identified target that has so far never been explored for improving succinate production in this microorganism. This methodology therefore represents a powerful tool for the streamlined identification of strain engineering targets that can accelerate bioprocess optimisation.

• Item Type: Articles
• Additional Information: This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) Grant number: BB/R505523/1 and Industrial Biotechnology Innovation Centre grant number IBioIC grant number 2016-149.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Daly, Dr Ronan
• Authors: Cortada-Garcia, J., Daly, R., Alison Arnold, S., and Burgess, K.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2023 The Author(s)
• First Published: First published in Scientific Reports 13:12990
• Publisher Policy: Reproduced under a Creative Commons license