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Corynebacterium glutamicum is a Gram-positive, anaerobic, rod-shaped soilbacterium able to grow on a diversity of carbon sources like sugars and organicacids. It is a biotechnological relevant organism because of its highlyefficient ability to biosynthesize amino acids, such as L-glutamic acid andL-lysine. Here, we reconstructed the most complete C. glutamicum regulatorynetwork to date and comprehensively analyzed its global organizationalproperties, systems-level features and functional architecture. Our analysesshow the tremendous power of Abasy Atlas to study the functional organizationof regulatory networks. We created two models of the C. glutamicum regulatorynetwork: all-evidences (containing both weak and strong supported interactions,genomic coverage = 73%) and strongly-supported (only accounting for stronglysupported evidences, genomic coverage = 71%). Using state-of-the-artmethodologies, we prove that power-law behaviors truly govern the connectivityand clustering coefficient distributions. We found a non-previously reportedcircuit motif that we named complex feed-forward motif. We highlighted theimportance of feedback loops for the functional architecture, beyond whetherthey are statistically over-represented or not in the network. We show that thepreviously reported top-down approach is inadequate to infer the hierarchygoverning a regulatory network because feedback bridges different hierarchicallayers, and the top-down approach disregards the presence of intermodular genesshaping the integration layer. Our findings all together further support adiamond-shaped, three-layered hierarchy exhibiting some feedback betweenprocessing and coordination layers, which is shaped by four classes ofsystems-level elements: global regulators, locally autonomous modules, basalmachinery and intermodular genes.

journal of biotechnology

Functional architecture and global properties of the Corynebacterium  glutamicum regulatory network: novel insights from a dataset with a high  genomic coverage