Figure 6. An integrated view of growth optimization for aaRSs.

At growth optimized levels of aaRS production (vertical dashed line), tRNA charging is not yet maximized. However, further increasing aaRS production and tRNA charging does not result in faster translation elongation, leading to no fitness benefit during overproduction. The native levels of aaRS production, with just enough capacity for the amino acid flux into protein synthesis, are positioned near the edge of the fitness cliff in the highly asymmetric landscape. The sharp sensitivity to aaRS underproduction is partially alleviated by the stringent response despite the unnecessary activation of amino acid biosynthesis genes in rich media. Furthermore, the T box-based autoregulation buffers perturbations to aaRS production from both directions, which is enabled by having non-maximized tRNA charging at the native levels.