Optimal proteome allocation strategies for phototrophic growth in a light-limited chemostat

Background: Cyanobacteria and other phototrophic microorganisms allow to couple the light-driven assimilation of atmospheric CO2 directly to the synthesis of carbon-based products, and are therefore attractive platforms for microbial cell factories. While most current engineering efforts are performed using small-scale laboratory cultivation, the economic viability of phototrophic cultivation also crucially depends on photobioreactor design and culture parameters, such as the maximal areal and volumetric productivities. Based on recent insights into the cyanobacterial cell physiology and the resulting computational models of cyanobacterial growth, the aim of this study is to investigate the limits of cyanobacterial productivity in continuous culture with light as the limiting nutrient. Results: We integrate a coarse-grained model of cyanobacterial growth into a light-limited chemostat and its heterogeneous light gradient induced by self-shading of cells. We show that phototrophic growth in the light-limited chemostat can be described using the concept of an average light intensity. Different from previous models based on phenomenological growth equations, our model provides a mechanistic link between intracellular protein allocation, population growth and the resulting reactor productivity. Our computational framework thereby provides a novel approach to investigate and predict the maximal productivity of phototrophic cultivation, and identifies optimal proteome allocation strategies for developing maximally productive strains. Conclusions: Our results have implications for efficient phototrophic cultivation and the design of maximally productive phototrophic cell factories. The model predicts that the use of dense cultures in well-mixed photobioreactors with short light-paths acts as an effective light dilution mechanism and alleviates the detrimental effects of photoin-hibition even under very high light intensities. We recover the well-known trade-offs between a reduced light-harvesting apparatus and increased population density. Our results are discussed in the context of recent experimental efforts to increase the yield of phototrophic cultivation.