The catabolic nature of fermentative substrates influence proteomic rewiring in Escherichia coli under anoxic growth

During anaerobic batch fermentation by Escherichia coli, there is a decline in cell proliferation rates and a huge demand is placed on cellular proteome to cater its catabolic and anabolic needs under anoxic growth. Previous studies have established a direct relationship between E. coli growth rate and cellular ribosomal content for fast proliferating cells. In this study, we integrated experimental findings with a systemic coarse-grained model of proteome allocation, to characterize the physiological outcomes at slow growth rate during anaerobic fermentative catabolism of different glycolytic and non-glycolytic substrates. The anaerobic catabolism of substrates favored high ribosomal abundances at lower growth rates. Interestingly, a modification of previously discussed "growth law", the ratio of active to inactive ribosomal proteome was found to be linearly related to growth rate for cells proliferating in slow to moderate regime (growth rate < 0.8 h-1). Also, under nutrient- and oxygen-limited growth conditions, the proteome proportion allocated for ribosomal activity was reduced, and resources were channelized towards catabolic and metabolic activities to overcome the limitations imposed while uptake and metabolizing substrate. The energy intensive uptake mechanism or lower substrate affinity, expended more catabolic proteome, which reduced its availability to other cellular functions. Conclusively, the nature of catabolic substrates imposed either uptake limitation or metabolic limitation coupled with ribosomal limitation (arising due to anoxic and nutritional stress), which resulted in higher proteome expenditure leading to sub-optimal phenotype.