(243e) Nonlinear Dynamics of Poly(β-hydroxybutyrate) Production In Microorganisms

Poly(β-hydroxybutyrate) (PHB) is an organic polymer, which can be synthesized by many microorganisms under unbalanced growth conditions and which serves as internal energy and carbon reserve material. This bacterial polyester has useful properties for applications as thermoplastics, elastomers and adhesives and is biodegradable and biocompatible.

In the present paper focus is on nonlinear dynamics during PHB formation triggered by the underlying regulatory processes. Depending on the microorganism different patterns of behavior are observed. Focus is on Ralstonia eutropha (also known as Alcaligenes eutrophus and Cupriavidus necator) compared to Rhodosprillum rubrum.

PHB production in Ralstonia eutropha has been studied intensively in the past. Recently, the existence of multiple steady states and bistability in continuous cultures of R. eutropha has been discussed in the literature based on a simplified metabolic network leading to a simple cybernetic model [1], which assumes optimal regulation in view of limited resources. In the present paper, it is shown that the multiplicity/bistability region tends to vanish if a more detailed model is used, which is fitted to experimental data for PHB production and PHB consumption [2]. Our model is based on the hybrid cybernetic modeling approach which provides a systematic framework for dynamic model generation from metabolic flux analysis. It shows very good agreement with independent experimental data over a wide range of operating conditions.

Different patterns of behavior are observed for Rhodospirillum rubrum. Depending on the ambient conditions R. rubrum is able to switch between respiratory and photosynthetic metabolism and thereby offers new perspectives for biotechnological production processes. Experimental data from microscopy and flow cytometry during growth on acetate reveal transient bimodal population dynamics in a batch reactor indicating bistability on the single cell level. An initially homogeneous population is segregating into a first subpopulation with only little amount of PHB and a second subpopulation with relatively high amount of PHB. Both subpopulations are merging again at later time points to build a homogeneous population again. Potential sources on the single cell level are discussed using metabolic flux analysis. Quantitative modeling approaches on the single cell level and their integration into the population level will be presented.

References:

1. M. A. Pinto, C. D. Immanuel, Sensitivity of bifurcation traits to model parameters in poly-beta-hydroxy butyrate production, In: ADCHEM 2006

2. A. Franz, H.-S. Song, D. Ramkrishna, A. Kienle, Experimental and theoretical analysis of poly(β-hydroxybutyrate) formation and consumption in Ralstonia eutropha, Bio. Eng. J. 55 (2011) pp. 49-58