A metabolism-centric proteomic map on the genomic scale: enabling functional annotation of the unknown genome

Understanding the biology of the metabolic network is key for biotechnology, where single cellular organisms such as budding yeast are used to produce proteins, vaccines or antibiotics. A metabolic network formed from similar reactions operates in mammalian cells, and changes during a lifetime being considered a main driver of ageing and age-associated disorders. Here we are applying for an industrial/academic partnership that will bring a new level into the understanding of this largest of all cellular systems, by creating an enzyme-centric quantitative map that spans the yeast genome. With our industrial partner Sciex, we establish a unique technological platform that can quantify 80% of metabolic enzymes in less than 30 minutes. We will apply this platform to measure enzymes in a collection of ~4800 yeast strains, each of which is lacking one gene at a time. In this way, we connect the majority of all genes in the genome with the metabolites and metabolic enzymes they affect. This map will be the most comprehensive investigation into a eukaryotic proteome conducted so far, and address both already known genes, and genes for which there is only little or no functional information so far available. We will learn about the function of new genes in two ways, first by studying their direct impact on the proteome and metabolism, and by associating them with the already known genes on the basis of their proteomic footprint. For these reasons, the project is of unique value to the mass spec manufacturing industry, that seeks possibilities to bring proteomic technology into environmental analytics, to biotechnology, that lacks information about metabolic networks so that they can exploit it for improving production cycles, and for basic science, that will gain unique insights into the function of novel genes and can use it to develop new strategies for addressing ageing-associated disease.