Optimization of Light and Nutrients Supply to Stabilize Long-Term Industrial Cultivation of Metabolically Engineered Cyanobacteria: A Model-Based Analysis

Metabolically engineered cyanobacteria are promising photosynthetic cell factories to produce valuable compounds in view of a bio-based industry. However, when the producer population is affected by a production burden, it usually experiences genetic instability leading to cells that lose the production capability, here defined as retro-mutants, which in the long-term take over the culture. Here we show that by exploitation of differences in nutrient and light use between these two phenotypes, in a continuous culture the operative conditions can be set to specifically select the producers. A mathematical model-based analysis used to investigate the effect of kinetic parameters shows that in specific combinations of their values, a continuous stirred-tank reactor (CSTR) can be operated to favor the producer's growth. The feasibility of the approach proposed is discussed in the context of literature data. On the basis of overall mass and energy balance analysis, a new approach to stabilize the producer phenotype in long-term industrial cultivation is proposed.