Grand Challenge in Membrane Biology: A systems biology study of the unicellular diazotrophic cyanobacterium Cyanothece sp. ATCC 51142

Cyanothece 51142 is a marine cyanobacterial strain notable for its ability to perform oxygenic photosynthesis and nitrogen fixation in the same single cell. These incompatible processes are temporally separated: photosynthesis is performed during the day and nitrogen fixation at night. As part of a complex diurnal cycle, these cells accumulate and subsequently mobilize storage inclusion bodies, specifically glycogen (carbon) and cyanophycin (nitrogen), making them natural biological batteries. In order to understand at a systems level how Cyanothece accomplishes these complex metabolic processes, we have undertaken a combination of ultrastructural, physiological, genomic, transcriptomic, proteomic, and metabolomic studies of this organism. High-resolution 3-D electron microscopy revealed that Cyanothece cells have a single extensive internal thylakoid membrane system. The genome of Cyanothece was sequenced (1) and found to contain a unique arrangement of one large circular chromosome, four small plasmids, and one linear chromosome. Global transcriptional analyses (2) uncovered 30% of genes with cyclic expression patterns and pinpointed a significant impact of nitrogen fixation on the diurnal cycle of different fundamental pathways. We have utilized the high- throughput accurate mass and time (AMT) tag approach to examine the proteome of Cyanothece 51142, and identified a total of 3,470 proteins with high confidence, which is approximately 65% of the predicted proteins based on the completely sequenced genome. These studies, as well as metabolite profiling, structural studies (3,4), and physiological measurements, when coupled with computational analysis and metabolic modeling, describe an organism in which tight control of cellular processes linked to storage of metabolic products for later usage is paramount for ecological success.