Less Genome, More Gain: Genome Reduction Enhances Transaminase-Producing E. coli in a Scale-Down Bioreactor

In large-scale bioprocesses, mixing limitations and design constraints cause the onset of heterogeneous environments, subjecting the cells to continuously changing external conditions, often reducing their performance compared to laboratory conditions. This study evaluated the performance in producing a heterologous transaminase (TA) of a genome-reduced Escherichia coli strain (RM214) in a STR-PFR scale-down system, benchmarking it against a wild-type strain. Under cycles of glycerol limitation and starvation, combined with oxygen limitation in later process stages, RM214 outperformed the wild-type strain. Due to its lower maintenance coefficient, RM214 showed a remarkable biomass increase of +53% and a boosted final volumetric activity with a +65% increase. These results were achieved with significantly reduced biomass-specific substrate uptake rates and respiratory parameters, both crucial for optimizing large-scale processes. This study underscores the applicability and enhanced robustness of genome-reduced strains in heterogeneous large-scale environments.