Metabolomics in Molecular Microbiology

Abstract

Because of the importance of microbes as model organisms, biotechnology tools, and contributors to mammalian pathology and ecosystem metabolism, there has been longstanding interest in measuring their metabolite levels. Current metabolomic methods, involving mass spectrometry-based measurement of cell extracts, enable routine quantitation of most central metabolites. Metabolomics alone, however, is inadequate to understand cellular metabolic activity: Flux measurement and proteomic, genetic, and biochemical approaches with a metabolomics bent are all needed. In this work, we first highlight examples where these integrated methods have contributed to discovery of metabolic pathways, regulatory interactions, and homeostasis mechanisms. We then describe a new metabolic regulatory paradigm and a novel metabolic pathway elucidated through a combination of metabolomics, molecular genetics, and physiological studies. We term this paradigm directed overflow metabolism. Finally, we use a combination of physiological studies and mass spectrometry to answer two outstanding questions of particular interest: excluding the role of ptsN in coordinating nitrogen and carbon metabolism, and the absence of arsenate in the DNA of arsenate-growth GFAJ-1 cells.