ArticleMicrobial cell factories2015
A particular silent codon exchange in a recombinant gene greatly influences host cell metabolic activity.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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13 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Recombinant expression of insoluble enzymes in Escherichia coli: a systematic review of experimental design and its manufacturing implications.Microbial cell factories · 2021Pooled it
- Primary high-throughput screening of engineered phytases by online monitoring of the oxygen transfer rate of Komagataella phaffii.Microbial cell factories · 2025Article
- Strategies for efficient production of recombinant proteins in Escherichia coli: alleviating the host burden and enhancing protein activity.Microbial cell factories · 2022Review
- Predicting high recombinant protein producer strains of Pichia pastoris MutScientific reports · 2022Article
- Recombinant protein production provoked accumulation of ATP, fructose-1,6-bisphosphate and pyruvate in E. coli K12 strain TG1.Microbial cell factories · 2021Article
- Scale-up fermentation of Escherichia coli for the production of recombinant endoglucanase from Clostridium thermocellum.Scientific reports · 2021Article
- Recombinant protein production associated growth inhibition results mainly from transcription and not from translation.Microbial cell factories · 2020Article
- Integration of Genetic and Process Engineering for Optimized Rhamnolipid Production UsingFrontiers in bioengineering and biotechnology · 2020Article
- Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology.Journal of visualized experiments : JoVE · 2017Article
- Prediction ofJournal of biological engineering · 2017Article
- Easy to use and reliable technique for online dissolved oxygen tension measurement in shake flasks using infrared fluorescent oxygen-sensitive nanoparticles.Microbial cell factories · 2016Article
- Respiration activity monitoring system for any individual well of a 48-well microtiter plate.Journal of biological engineering · 2016Article
- The Rare Codon AGA Is Involved in Regulation of Pyoluteorin Biosynthesis in Pseudomonas protegens Pf-5.Frontiers in microbiology · 2016Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecombinant 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.
resultsHost stain metabolic burden correlates with recombinant protein production. Upon heterologous gene expression, tremendous differences in respiration, biomass and protein production were observed. According to their different respiration activity the E. coli clones could be classified into two groups, Type A and Type B. Type A clones tended to higher product formation, Type B clones showed stronger biomass formation. Whereas codon usage and intracellular nucleobases had no influence on the Type-A-Type-B-behavior, plasmid copy number, mRNA content and carbon source consumption strongly differed between the two groups.
conclusionsParticular silent codon exchanges in a heterologous gene sequence led to differences in initial growth of Type A and Type B clones. Thus, the biomass concentration at the time point of induction varied. In consequence, not only plasmid copy number and expression levels differed between the two groups, but also the kinetics of lactose and glycerol consumption. Even though the underlying molecular mechanisms are not yet identified we observed the astonishing phenomenon that particular silent codon exchanges within a heterologous gene tremendously affect host cell metabolism and recombinant protein production. This could have great impact on codon optimization of heterologous genes, screening procedures for improved variants, and biotechnological protein production processes.
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