Understanding and mathematical modelling of cellular resource allocation in microorganisms: a comparative synthesis

BACKGROUND: The rising consensus that the cell can dynamically allocate its resources provides an interesting angle for discovering the governing principles of cell growth and metabolism. Extensive efforts have been made in the past decade to elucidate the relationship between resource allocation and phenotypic patterns of microorganisms. Despite these exciting developments, there is still a lack of explicit comparison between potentially competing propositions and a lack of synthesis of inter-related proposals and findings. RESULTS: In this work, we have reviewed resource allocation-derived principles, hypotheses and mathematical models to recapitulate important achievements in this area. In particular, the emergence of resource allocation phenomena is deciphered by the putative tug of war between the cellular objectives, demands and the supply capability. Competing hypotheses for explaining the most-studied phenomenon arising from resource allocation, i.e. the overflow metabolism, have been re-examined towards uncovering the potential physiological root cause. The possible link between proteome fractions and the partition of the ribosomal machinery has been analysed through mathematical derivations. Finally, open questions are highlighted and an outlook on the practical applications is provided. It is the authors’ intention that this review contributes to a clearer understanding of the role of resource allocation in resolving bacterial growth strategies, one of the central questions in microbiology. CONCLUSIONS: We have shown the importance of resource allocation in understanding various aspects of cellular systems. Several important questions such as the physiological root cause of overflow metabolism and the correct interpretation of ‘protein costs’ are shown to remain open. As the understanding of the mechanisms and utility of resource application in cellular systems further develops, we anticipate that mathematical modelling tools incorporating resource allocation will facilitate the circuit-host design in synthetic biology.