Toward a systems-level understanding of gene regulatory, protein interaction, and metabolic networks in cyanobacteria.

Cyanobacteria are essential primary producers in marine ecosystems, playing an important role in both carbon and nitrogen cycles. In the last decade, various genome sequencing and metagenomic projects have generated large amounts of genetic data for cyanobacteria. This wealth of data provides researchers with a new basis for the study of molecular adaptation, ecology and evolution of cyanobacteria, as well as for developing biotechnological applications. It also facilitates the use of multiplex techniques, i.e., expression profiling by high-throughput technologies such as microarrays, RNA-seq, and proteomics. However, exploration and analysis of these data is challenging, and often requires advanced computational methods. Also, they need to be integrated into our existing framework of knowledge to use them to draw reliable biological conclusions. Here, systems biology provides important tools. Especially, the construction and analysis of molecular networks has emerged as a powerful systems-level framework, with which to integrate such data, and to better understand biological relevant processes in these organisms. In this review, we provide an overview of the advances and experimental approaches undertaken using multiplex data from genomic, transcriptomic, proteomic, and metabolomic studies in cyanobacteria. Furthermore, we summarize currently available web-based tools dedicated to cyanobacteria, i.e., CyanoBase, CyanoEXpress, ProPortal, Cyanorak, CyanoBIKE, and CINPER. Finally, we present a case study for the freshwater model cyanobacteria, Synechocystis sp. PCC6803, to show the power of meta-analysis, and the potential to extrapolate acquired knowledge to the ecologically important marine cyanobacteria genus, Prochlorococcus

Extracellular proteins: Novel key components of metal resistance in cyanobacteria?

Metals are essential for all living organisms and required for fundamental biochemical processes. However, when in excess, metals can turn into highly-toxic agents able to disrupt cell membranes, alter enzymatic activities and damage DNA. Metal concentrations are therefore tightly controlled inside cells, particularly in cyanobacteria. Cyanobacteria are ecologically relevant prokaryotes that perform oxygenic photosynthesis and can be found in many different marine and freshwater ecosystems, including environments contaminated with heavy metals. As their photosynthetic machinery imposes high demands for metals, homeostasis of these micronutrients has been widely studied in cyanobacteria. So far, most studies have focused on how cells are capable of controlling their internal metal pools, with a strong bias towards the analysis of intracellular processes. Ultrastructure, modulation of physiology, dynamic changes in transcription and protein levels have been studied, but what takes place in the extracellular environment when cells are exposed to an unbalanced metal availability remains largely unknown. The interest in studying the subset of proteins present in the extracellular space has only recently begun and the identification and functional analysis of the cyanobacterial exoproteomes are just emerging. Remarkably, metal-related proteins such as the copper-chaperone CopM or the iron-binding protein FutA2 have already been identified outside the cell. With this perspective, we aim to raise the awareness that metal-resistance mechanisms are not yet fully known and hope to motivate future studies assessing the role of extracellular proteins on bacterial metal homeostasis, with a special focus on cyanobacteria