of the growth medium in the absence

of the growth medium in the absence of the antibiotic (Fig. 3A).
The tRNA-affiliated fraction ϕT also increases, being forced to
do so by the assumption of coregulation (Fig. 3C). We note that
in the four-component model, translation limitation can also be
obtained by increasing the Michaelis constant of translation φM,
which leads to the same growth-rate dependence as changing the
maximal translation speed γmax.
Coregulation of Ribosomal and tRNA-Affiliated Proteins Corresponds
to Near-Optimal Allocation of Protein Synthesis Resources. So far, we
have assumed that the factor α, the ratio between the tRNAaffiliated
and ribosomal proteome fractions, is constant and independent
of the growth rate. Based on an optimization scheme
originally proposed by Ehrenberg and Kurland (22), we have
varied α and adjusted it such that the growth rate is maximized
for any given growth conditions, i.e., for fixed medium parameters
(ν, γmax, φM). The optimal α is dependent on the growth rate
and a systematic decrease of the ratio of T-proteins to ribosomes
with the growth rate is obtained (Fig. 4). Although the data for
EF-Tu per ribosome (symbols in Fig. 4C) show a slight decrease
with increasing growth rate, the optimal α is smaller than the
observed values. However, for all realistic values of the growth
rate (up to three doublings per hour), a constant α = 0.6 as used
above leads to a growth rate within 10%of the maximum obtained
by optimizing α, and the experimental ratio of EF-Tu per ribosome,
which decreases slightly at fast growth, even remains in
the ±5% region (gray symbols in Fig. 4C). As a result, we conclude
that coregulation (or approximate coregulation) of ribosomal
and T-proteins is a near-optimal strategy for the cell, which
may be “good enough” to achieve fast growth. As the additional
complexity of regulating the two proteome sectors separately to
achieve full optimization may incur additional fitness costs,
coregulation (with possibly some adjustment to lower the ratio
ϕT/ϕR at fast growth) may even be the most robust strategy for
the cell to adopt.