Field of atom mapping of metabolic networks is lacking an automated approach, which accounts for the information of reaction mechanism for atom mapping and is extendable from atom-mapped reactions to atom-mapped reaction networks. We developed “iAM.NICE” (in silico Atom Mapped Network Integrated Computational Explorer), for the atom-level reconstruction of metabolic networks from the in silico labeled substrates to elucidate the mass flow in a biochemical reaction network. “iAM.NICE” transfers the label(s) from a substrate to a product by taking into account the information about the rearrangements of the chemical bonds derived from the “generalized reaction rules” introduced in BNICE.ch [1] . It uses the 582 reaction rules that cover the reconstruction of ~ 90% of known enzymatic reactions (KEGG database). The originality of “iAM.NICE” stems from two aspects: the first automated atom-mapping algorithm that is derived from the underlying enzymatic biotransformation mechanism. its application is not limited to individual reactions and it can be used for the reconstruction of atom-mapped metabolic networks.