Abstract
BackgroundAlthough much is understood about the enzymatic cascades that underlie cellular biosynthesis, comparatively little is known about the rules that determine their cellular organization. We performed a detailed analysis of the localization of E.coli GFP-tagged enzymes for cells growing exponentially.ResultsWe found that out of 857 globular enzymes, at least 219 have a discrete punctuate localization in the cytoplasm and catalyze the first or the last reaction in 60% of biosynthetic pathways. A graph-theoretic analysis of E.coli’s metabolic network shows that localized enzymes, in contrast to non-localized ones, form a tree-like hierarchical structure, have a higher within-group connectivity, and are traversed by a higher number of feed-forward and feedback loops than their non-localized counterparts. A Gene Ontology analysis of these enzymes reveals an enrichment of terms related to essential metabolic functions in growing cells. Given that these findings suggest a distinct metabolic role for localization, we studied the dynamics of cellular localization of the cell wall synthesizing enzymes in B. subtilis and found that enzymes localize during exponential growth but not during stationary growth.ConclusionsWe conclude that active biochemical pathways inside the cytoplasm are organized spatially following a rule where their first or their last enzymes localize to effectively connect the different active pathways and thus could reflect the activity state of the cell’s metabolic network.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-014-0131-1) contains supplementary material, which is available to authorized users.
Highlights
Much is understood about the enzymatic cascades that underlie cellular biosynthesis, comparatively little is known about the rules that determine their cellular organization
E.coli enzymes in the first and last position of pathways preferentially localize to cytoplasmic foci The complex organization of the bacterial cytoplasm suggests that enzymes could, freely diffuse, and show spatial ordering in the cytoplasm
As the KEGG collection, a set of manually drawn pathway maps indicating molecular interactions and reactions networks, indicates that E.coli K-12 MG1655 has 857 enzymes involved in known metabolic reactions, at least 25% of the enzymes in E.coli cells growing exponentially show a discrete punctuate localization at diverse locations of the cytoplasm
Summary
Much is understood about the enzymatic cascades that underlie cellular biosynthesis, comparatively little is known about the rules that determine their cellular organization. It is possible that the existence of large multi-enzyme complexes, as opposed to freely diffusing enzymes, could either be determined by constraints limited to highly specialized reactions, or a general mechanism used throughout the cell to achieve a generic metabolic function. Supporting the latter option, the hypothesis of metabolic channeling proposes that reaction products in a metabolic pathway move from one active site to another within tightly associated multi-enzyme complexes.
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