On-line targeted metabolomics for real-time monitoring of relevant compounds in fermentation processes

Fermentation monitoring is a powerful tool for bioprocess development and optimization. On-line metabolomics is a technology that is starting to gain attention as a bioprocess monitoring tool, allowing the direct measurement of many compounds in the fermentation broth at a very high time resolution. In this work, targeted on-line metabolomics was used to monitor 40 metabolites of interest during three Escherichia coli succinate production fermentation experiments every 5 min with a triple quadrupole mass spectrometer. This allowed capturing high-time resolution biological data that can provide critical information for process optimization. For nine of these metabolites, simple univariate regression models were used to model compound concentration from their on-line mass spectrometry peak area. These on-line metabolomics univariate models performed comparably to vibrational spectroscopy multivariate partial least squares regressions models reported in the literature, which typically are much more complex and time consuming to build. In conclusion, this work shows how on-line metabolomics can be used to directly monitor many bioprocess compounds of interest and obtain rich biological and bioprocess data. In this work, targeted on-line metabolomics was used to directly monitor 40 process-relevant compounds during three Escherichia coli succinate production fermentation experiments every 5 min with a triple quadrupole mass spectrometer. Cortada-Garcia and co-workers describe how this novel process analytical technologies tool allows to easily obtain rich biological and bioprocess data with little post-acquisition data treatment.image