Systems-Wide Prediction of Enzyme Promiscuity Reveals a New Underground Alternative Route for Pyridoxal 5’-Phosphate Production in E. coli
Fig 1
Schematic of prediction framework for promiscuous replacers.
(1) Gene similarity trees are built around each gene in E. coli, including any distantly related gene in the RAST database. (2) A matrix is formed which links genes with their primary functions and also potential promiscuous functions. A gene (in this example, eco1) will take a potential secondary ‘promiscuous’ function in the matrix if its similarity tree includes any genes annotated with different functions (e.g., in this example, shi4, which encodes function fn4). (3) Cases in which a gene’s predicted promiscuous function is identical to the function of another gene in E. coli constitute predicted ‘direct’ target-replacer gene pairs (via PROPER). We also predict ‘indirect’ target-replacer pairs where a replacer bypasses the target’s function (via GEM-PROPER). (4) Promiscuous activity of a ‘replacer’ gene can be confirmed for target-replacer pairs in which the target is conditionally essential on a minimal medium, via the multicopy suppression assay.