Increasing production yield of tyrosine and mevalonate through inhibition of biomass formation

Microbial cell factories have been engineered to produce a variety of biochemicals, ranging from biofuels, food addtives to pharmaceuticals. However, for most compounds, the production yield is far from reaching economical targets. Accumulation of excess biomass contributes to decreasing production yields, and a method for limiting biomass formation while allowing for continued production of biochemicals is therefore desirable. In this study, we investigated eight different culturing setups aiming at inhibiting biomass formation of Escherichia coli, based on nutrient limitations or the addition of growth inhibitors. The ability to control cell growth and the production of biochemicals, exemplified by mevalonate and tyrosine, was characterized. An increased mass yield of both mevalonate and tyrosine was achieved by limiting phosphate, sulfate or magnesium in the media. Sulfate limitation, in particular, resulted in an increase in mass yield of mevalonate and tyrosine by 80% and 50%, respectively. By tracking production and biomass concentrations, it was observed that the production was maintained for more than 10 h after inhibition of cell growth, despite cell maintenance requirements. The outlined method serves as promising approach for increasing production yield of a range of different biochemicals.