TY - JOUR AU - Rahmen, Natalie AU - Schlupp, Christian D. AU - Mitsunaga, Hitoshi AU - Fulton, Alexander AU - Aryani, Tita AU - Esch, Lara AU - Schaffrath, Ulrich AU - Fukuzaki, Eiichiro AU - Jaeger, Karl-Erich AU - Büchs, Jochen PY - 2015 DA - 2015/10/05 TI - A particular silent codon exchange in a recombinant gene greatly influences host cell metabolic activity JO - Microbial Cell Factories SP - 156 VL - 14 IS - 1 AB - Recombinant protein production using Escherichia coli as expression host is highly efficient, however, it also induces strong host cell metabolic burden. Energy and biomass precursors are withdrawn from the host’s metabolism as they are required for plasmid replication, heterologous gene expression and protein production. Rare codons in a heterologous gene may be a further drawback. This study aims to investigate the influence of particular silent codon exchanges within a heterologous gene on host cell metabolic activity. Silent mutations were introduced into the coding sequence of a model protein to introduce all synonymous arginine or leucine codons at two randomly defined positions, as well as substitutions leading to identical amino acid exchanges with different synonymous codons. The respective E. coli clones were compared during cultivation in a mineral autoinduction medium using specialized online and offline measuring techniques to quantitatively analyze effects on respiration, biomass and protein production, as well as on carbon source consumption, plasmid copy number, intracellular nucleobases and mRNA content of each clone. SN - 1475-2859 UR - https://doi.org/10.1186/s12934-015-0348-8 DO - 10.1186/s12934-015-0348-8 ID - Rahmen2015 ER -