BN Seminar

Abstract

Our knowledge about molecular regulation events and their organization into larger regulation networks increases steadily, but we are much less informed about the functionality of individual regulation events and their quantitative relevance for controlling a given biological function and eventually a phenotype. For metabolism this function is the flux of small molecules, the coordination of which in metabolic networks may be achieved through a variety of overlapping regulation mechanism (1). Out of the bewildering complexity of possible regulatory interactions, generally only very few matter for a given organism and condition, and the regulatory logic of this regulation is usually highly similar in different microbes, although the molecular implementation might differ (2). In this lecture I will describe how we delineate such regulation events that actively control the coordination of metabolic fluxes in E. coli and yeast by combining various omics methods, ¹³C-flux analysis and computational modelling. I will present evidence that transcriptional regulation plays a much less important role in controlling pathway fluxes than previously thought because most enzymes are more abundant than necessary to carry out their function (3, 4). Instead we find enzyme phosphorylation (5) and allosteric metabolite-enzyme interactions (6) to be much more important in controlling primary metabolism.

References:

1. Gerosa & Sauer. Curr Opin Biotechnol 22:566 (2011)
2. Chubukov, Gerosa, Kochanowski & Sauer. Nat Rev Microbiol 12: 327 (2014)
3. Kochanowski, Sauer & Chubukov. Curr Opin Biotechnol 24: 987 (2013)
4. Chubukov et al. Mol Sys Biol 9: 709 (2013)
5. Oliveira et al. Mol Sys Biol 8:623 (2012)
6. Link et al. Nature Biotechnol 31:357-61 (2013)