Engineering microbial cell viability for enhancing chemical production by second codon engineering

Microbial cell factories offer a promising strategy for the sustainable production of industrial chemicals from renewable biomass feedstock. However, their performance is often limited by poor microbial cell viability (MCV). Here, MCV was engineered to enhance chemical production by optimizing the regulation of lifespan-specific genes to reduce the accumulation of reactive oxygen species (ROS). In Escherichia coli, MCV was improved by reducing ROS accumulation using second codon engineering to regulate hypoxia-inducible transcription factor (arcA), resulting in lysine production up to 213 g L−1 with its productivity 5.90 g L−1·h−1. In Saccharomyces cerevisiae, MCV was increased by decreasing ROS accumulation using second codon engineering to fine-tune ceramide synthase (lag1), leading to glucaric acid production up to 9.50 g L−1 with its productivity 0.057 g L−1·h−1. These results demonstrate that engineering MCV is a potential strategy to boost the performance of microbial cell factories in industrial processes.