Growth-associated synthesis of poly(hydroxybutyric acid) in Methylobacterium rhodesianum as an expression of an internal bottleneck

Methylobacterium rhodesianum MB126 growing on fructose accumulates poly(hydroxybutyric acid) (PHB) during exponential growth in contrast to growth on methanol, where the strain accumulates the polyester in response to limitation of several growth factors. A mathematical description of the kinetics, based on the growth-associated term of product formation, yields a good correlation to the experimental data, as it is validated by the course of PHB content after the substrate shift from methanol to fructose. From a comparison of carbon fluxes with enzyme capacities, we assume a bottleneck in the tricarboxylic acid cycle to be the reason for the growth-associated PHB synthesis. PHB formation from fructose, which can be considered as a kind of fermentation, helps overcome the bottleneck. This hypothesis is supported by the fact that the simultaneous PHB synthesis can be suppressed by an additional supply of NADH via the oxidation of formate.