Proteomes reflect size-based growth constraints across diverse microbes

The maximum growth rate of microbes plays a central role in shaping ecological outcomes and is a major target of bioengineering efforts. Previous data compilations suggest single cell maximum growth rates mostly decrease with cell volume across species, except for an initial increase from the very smallest microbes to an intermediate size. Here we hypothesized that this unimodal relationship is shaped by the volumetric requirements of ribosomes and the surface area-dependence of nutrient supply. We developed a mechanistic model relating ribosomal protein mass fraction to growth rate and cell size. Predictions from this model were empirically supported by proteomic data from 97 prokaryotes ranging over 3 orders of magnitude in cell volume. Our analysis suggests that the smallest cells' growth rates are restricted by the volumetric constraints on ribosomes per cell and rely on compact, heterotrophic metabolisms. In contrast, growth rates of the largest prokaryotes face geometric constraints on specific resource acquisition rates, capping growth rates and investment in ribosomal protein, but allowing investment in protein-expensive metabolisms including phototrophy and sulfur oxidation. Prokaryotic cells of intermediate size face neither constraint and exhibit a higher maximum growth rate potential, which, we hypothesize, is associated with elevated metabolic diversity.