Probing the complex system of metabolic integration

Since its inception, microbial physiology has evolved rapidly to accommodated the driving force of the newest available technologies, upon which the field depends. In the early history of metabolic studies, physiology focused primarily on identifying and classifying microbes based on the properties of the whole microbial cell. A microbe's physiology was defined by its habitat, cellular morphology, and metabolic capacities, including resource utilization and waste production. Subsequently, molecular approaches were implemented to under stand the details of metabolic components and results from these studies amassed the majority of information that we associate with metabolic knowledge today. Over the last similar to 15 years, technological innovations have facilitated the generation of data that can provide a global view of various cellular components. These technological approaches lack the means to define the function and integration of metabolic components beyond those predicted by computational programs, which are based on prior knowledge. Presented herein is the rationale for a global genetic strategy that has been used in the analysis of metabolic integration in Salmonella enterica. A central premise of this work is that metabolic integration can be perceived as a complex system and, as such, concepts defined for complex systems can be brought to bear oil understanding metabolism. The long-term goal of the reported work is to define the components and connections of metabolism to a degree that systems theory call be applied to model microbial metabolism. What is presented herein is a progress report meant to illustrate the basics of the approach, the type of results that can be generated, and how they can clarify the framework of complexity underlying metabolism. It is hoped that the reader will consider the value of this approach and appreciate the intellectual excitement that can be generated by a journey to define uncharacterized metabolic components and connections.