Metabolic modeling as a tool for evaluating polyhydroxyalkanoate copolymer production in plants

The production of polyhydroxyalkanoates in plants is an interesting commercial prospect due to lower carbon feedstock costs and capital investments. The production of poly-(3-hydroxybutyrate) has already been successfully demonstrated in plant plastids, and the production of more complex polymers is under investigation. Using a mathematical simulation model this paper outlines the theoretical prospects of producing the copolymer poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-3HV)] in plant plastids. The model suggests that both the 3HV/3HB ratio and the copolymer production rate will vary considerably between dark and light conditions. Using metabolic control analysis we predict that the beta-ketothiolase predominately controls the copolymer production rate, but that the activity of all three enzymes influence the copolymer ratio. Dynamic simulations further suggest that controlled expression of the three enzymes at different levels may enable desirable changes in both the copolymer production rate and the 3HV/3HB ratio. Finally, we illustrate that natural variations in substrate and cofactor levels may have a considerable impact on both the production rate and the copolymer ratio, which must be taken into account when constructing a production system.