Photosynthetic Bioplastics Production with Cyanobacteria by Coupled Growth-Production Mutants

In this work, we study PHB direct production (without a heterotrophic step) using Synechocystis sp PCC 6803 within a Systems Metabolic Engineering approach. We consider a GEnome-scale Model (GEM) of the cyanobacteria, developed in previous work, and use it to couple growth with PHB production by finding genetic interventions (knock-outs) that make PHB production essential for growth. This is achieved by formulating a bilevel-programming problem, in which the knock-outs are represented by binary variables related to the genes of the GEM. After reformulation based on duality theory, a Mixed Integer Linear Programming (MILP) problem is obtained and solved in GAMS. A mutant that completely couples biopolymer production with growth in Synechocystis is obtained, and its flux distributions under exponential growth conditions are analysed by Flux Balance Analysis (FBA). Numerical results provide useful insights on sustainable photosynthetic bioplastics production with cyanobacteria.