PhD ceremony Mr. T.H. Eckhar: Lactococcus lactis systems biology. A characterization at different growth rates

PhD ceremony: Mr. T.H. Eckhardt, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Lactococcus lactis systems biology. A characterization at different growth rates

Promotor(s): prof. O.P. Kuipers, prof. J. Kok

Faculty: Mathematics and Natural Sciences

The thesis of Thomas Eckhardt describes a systems biology approach to explain the fermentative behavior of Lactococcus lactis, grown at specific varying growth rates. When cells of L. lactis were grown at varying growth rates in chemostats, under glucose limiting conditions, the bacteria employ a metabolic shift from mixed-acid to homolactic fermentation. The hypothesis for Eckhardts study was that this metabolic shift is based on the predictions of the self-replicator model, which presumes that there is a tradeoff between investments in enzyme synthesis and metabolic yields for alternative catabolic pathways. The thesis of Eckhardt provides a comprehensive and high-quality dataset of mRNA and protein ratios and enzyme activities of most of the glycolytic enzymes. The data from his study show that the transcription of the genes encoding glycolytic enzymes remains equal with increasing growth rate. Also the protein levels and the kinetics of the glycolytic pathway enzymes hardly change when the growth rate changes. Yet, the metabolic flux data show that under the growth rate-controlled conditions examined, a metabolic shift from mixed-acid to homolactic fermentation is established. Thus, the theory of protein investment as a means to optimize the expressed proteins to the growth rate, does not explain the metabolic shift in L. lactis.

Next to that, Eckhardt details the regulation of fatty acid biosynthesis in L. lactis as well as the role of a protein (YfiA) that is responsible for ribosome dimerization. From an industrial perspective, this data is useful for further optimization of L. lactis as a microbial cell factory and for choosing the best growth conditions, while retaining desired properties.