A Roadmap Towards a Systems Biology Description of Bacterial Nitrogen Fixation

Abstract

Nitrogen fixation is a process in which microorganisms transform atmospheric nitrogen, N2, into ammonia, NH3. Various microorganisms can perform nitrogen fixation, including most of the Rhizobiaceae family, several cyanobacteria, certain gram-positive bacteria, and gammaproteobacteria, as well as a select archaea. In general, this process plays a significant role in maintaining nitrogen balance in higher organisms and in the biosphere. Nitrogen fixation in Rhizobiaceae bacteria has been studied extensively, particularly in symbiotic association with legume plants. These studies have focused on the genetic, regulatory, and metabolic mechanisms of nitrogen fixation and their potential use in developing natural bio-fertilizers, which is an important application for sustainable agricultural programs. With the advent of high-throughput technologies, new conceptual approaches are required to understand the metabolic activity supporting this biological process and to uncover its principles in a holistic and systematic fashion. Thus, together with genome-scale data, there are useful computational frameworks for organizing high-throughput data and interpreting complex metabolic processes such as nitrogen fixation. For example, constraint-based modeling provides a systems biology framework for characterizing, understanding, and predicting the metabolic phenotypes that support nitrogen fixation in bacteria. Notably, these computational analyses are capable of exploring a wide range of fundamental and practical issues, such as evaluating the role of metabolic pathways in bacterial nitrogen fixation and designing new strains of microorganisms with improved nitrogen-fixing activity. Specifically, in this chapter we show that genome-scale metabolic modeling of nitrogen fixation in Rhizobium etli during its association with the legume Phaseolus vulgaris (common bean plant) can serve as an optimal guide for the following (1) integrating experimental data, (2) describing metabolic activity during nitrogen fixation, and (3) designing experiments to survey genotype–phenotype relationships in nitrogen fixation.