Robust productivity in industrial fermentations: Regulation of phosphofructokinase activity through easily measurable, critical nutrient ratio

A comprehensive optimization of fermentation processes is non-trivial due to the interdependence of individually well-studied fermentation parameters. Two such important parameters are the oxygen uptake rate (OUR) and the ratio of two critical nutrients (CNR) in the broth. Since CNR is easily measurable, it was investigated for its efficacy in process optimization. Phosphofructokinase activity (PFK) was used as a supplementary marker of productivity. The strong correlations between the above parameters motivated optimization of fermentations using four industrially useful microbes: Escherichia coli, Pichia pastoris, Streptomyces species and Aspergillus niger. The relevance of CNR was independent of dissolved oxygen and nutrient sources, even though the nutrient release and its consequent availability depended upon the nutrient type and source. Planned changes in CNR lead to a 3 fold and a 3–5 fold increase in PFK and specific productivity respectively. The ATP and citrate levels beyond 2.5 mmol (g cell)−1 inhibited PFK. A mathematical model was developed to explain the relationship between PFK and its effectors: CNR, ATP, and citrate. By optimizing CNR, the respective maximum productivities were increased by a minimum of 34%, 100%, 57% and 30% compared to the respective controls for above processes.

► Nutrient ratio (NR) regulates microbial phosphofructokinase activity (PFK).
► Relevance of NR was found to be independent of the type of nutrients tested.
► NR–PFK–oxygen uptake link was studied for Aspergillus niger, Streptomyces species, Pichia pastoris, Escherichia coli.
► Optimization of NR significantly improved microbial specific productivity.
► PFK was modeled as a function of nutrient ratio, ATP and an inhibitor citrate.