Genomic principles for feedback regulation of metabolism
Nick Luscombe, PhD
European Bioinformatics Institute
Wellcome Trust Genome Campus
Cambridge, UK
Small molecule metabolism is the highly coordinated interconversion of chemical substrates through enzyme-catalysed reactions. It is central to the viability of all organisms as it enables the assimilation of nutrients for energy production and the synthesis of precursors for all cellular components. The system is tightly regulated so cells can respond efficiently to environmental changes. This is optimised to minimise the substantial cost of enzyme production and core metabolite depletion, and to maximise the benefit of cell growth and division. It is commonly known that this regulation is achieved by controlling either (i) the availability of enzymes or (ii) their activities. Though the molecular mechanisms behind these two regulatory processes have been elucidated in great detail, and we still lack insight into how they are deployed and complement each other at a global level. Here, I will present a genome-scale analysis of how regulatory feedback by small molecules control the metabolic system, and examine how the two modes of regulation are deployed throughout the system.