TY - JOUR
T1 - Streamlined identification of strain engineering targets for bioprocess improvement using metabolic pathway enrichment analysis
AU - Cortada Garcia, Joan
AU - Daly, Rónán
AU - Arnold, S. Alison
AU - Burgess, Karl
N1 - Funding Information:
This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) grant number BB/R505523/1 and the Industrial Biotechnology Innovation Centre (IBioIC), grant number 2016-149. We want to thank Ingenza Ltd. for kindly providing the process details and medium recipe, and particularly to Scott Baxter for providing the succinate producer BW25113 E. coli strain and Fraser Brown, Iain McKean and Philip Weyrauch for running the off-line HPLC-UV/Vis-RI analysis of the fermentation samples. We also want to thank Glasgow Polyomics, especially Erin Manson, Hannah Rankin, Suzanne McGill and Stefan Weidt for running the LC-MS samples on the Q Exactive Orbitrap mass spectrometer. TM
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/8/10
Y1 - 2023/8/10
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-023-39661-x
DO - 10.1038/s41598-023-39661-x
M3 - Article
SN - 2045-2322
VL - 13
JO - Scientific Reports
JF - Scientific Reports
M1 - 12990
ER -