CeBiTec Colloquium

 date 

Monday, January 31st 2011, 17 c.t.

 location 

G2-104, CeBiTec Building

 speaker 

Dr. Katharina Nöh

Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich

title 

A Universal Tool for Measuring in vivo Metabolic Activities:
13C-Metabolic Flux Analysis with Isotope Labeling Experiments

  To deeply understand an organisms’ metabolism is indispensable when aiming at an increased productivity under industrially relevant conditions. Nowadays a variety of high-throughput omics-tools comprising genomic and metagenomic sequencing, transcriptome, proteome, and metabolome profiling become available generating a vast amount of data. The functional end point of the (mostly unknown non-linear) relations between these ‘ome’ layers, however, is the entirety of all metabolic flux rates (the fluxome). In combination with the set of small-molecule metabolites (the metabolome), the fluxome reflects the cells’ in vivo metabolic activity.
While metabolome data can be directly accessed, the intracellular in vivo metabolic fluxes have to be indirectly inferred from measured quantities and biochemical network models with the aid of computational tools. Currently the most reliable method for determining these unobservable reaction rates in a metabolically steady state is metabolic flux analysis with 13C-labeling experiments (13C MFA): A defined 13C labeled substrate is incorporated into the carbon backbone of a wide range of metabolites. The distribution of labeled carbon traversing along metabolic pathways generates a characteristic imprint of labeling patterns whose mass signature is observed by highly sensitive and/ or selective measurement devices like GC-MS, LC-MS(/MS), and NMR. From the measurements (i.e. labeling patterns and extracellular rates) and balance equations, the absolute flux rates and metabolite concentrations are estimated. As part of an integrative data evaluation approach, 13C MFA facilitates direct and comprehensive insights into the active metabolic network of microbials, plants and even higher cells.
 host 

Prof. Dr. Thomas Noll