How genetic circuits can optimally tune metabolic protein concentrations

Since cells have finite biosynthetic resources for protein synthesis, a rise in one protein concentration is generally at the expense of that of others. A logical consequence is then that phenotypic traits trade-off: cells cannot excel at everything. They cannot grow fast and be very stress tolerant and adaptive to new conditions at the same time. Another consequence is that protein under- and over-expression without a long-term fitness benefit is likely selected against. 

How do cells then decide on the expression level of proteins? Can they even tune protein concentrations optimally — to prevent wasteful over-expression and suboptimal under-expression? What do cells try to achieve by changing protein concentrations? How can they decide that tuning is finished and that protein concentrations are optimal?

In this new paper (, we can gave an overview of how cell can achieve growth-rate-maximising tuning of metabolic protein concentrations, via optimal gene expression of metabolic genes. We pioneered this method in Berkhout et al.( and generalised it in Planqué et al. (, and applied its way of thinking to understand the regulation of ribosomal gene expression in E. coli in Bosdriesz et al. ( Here we give an elementary overview of this theoretical method. We apply it to understand the gene-regulatory feedback regulation of amino-acid metabolism. 

Some more background information on this way of thinking can also be found in some teaching material I wrote for a course on enzyme kinetics (

We hope that we have inspired you to think also about how cellular objectives can be achieved by gene-regulatory circuits.