Streamlining the Analysis of Dynamic C-Labeling Patterns for the Metabolic Engineering of As L-Histidine Production Host

Overview

Journal Metabolites

Publisher MDPI

Date 2020 Nov 17

PMID 33198305

Citations 3

Authors

Andre Feith

Andreas Schwentner

Attila Teleki

Lorenzo Favilli

Bastian Blombach

Ralf Takors

Affiliations

Soon will be listed here.

Abstract

Today's possibilities of genome editing easily create plentitudes of strain mutants that need to be experimentally qualified for configuring the next steps of strain engineering. The application of design-build-test-learn cycles requires the identification of distinct metabolic engineering targets as design inputs for subsequent optimization rounds. Here, we present the pool influx kinetics (PIK) approach that identifies promising metabolic engineering targets by pairwise comparison of up- and downstream C labeling dynamics with respect to a metabolite of interest. Showcasing the complex l-histidine production with engineered l-histidine-on-glucose yields could be improved to 8.6 ± 0.1 mol% by PIK analysis, starting from a base strain. Amplification of , , and formyl recycling was identified as key targets only analyzing the signal transduction kinetics mirrored in the PIK values.

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