The limited amount of fossil fuels shifted research in industry and academia towards sustainable production of their substitutes. One of the most prominent biofuel candidates is Methyl Ethyl Ketone (MEK), due to its thermo-physical and transport properties. Since there is no native producer of MEK, we used Biochemical Network Integrated Computational Explorer (BNICE.ch) to explore the space of biotransformations around it. Out of 1325 identified compounds one reaction step away from MEK we chose 5 for further study as they can be (i) chemically converted to MEK; (ii) used as precursor metabolites for other chemicals. We reconstructed 3’679’610 novel biosynthetic pathways up to 4 reaction steps from 157 central carbon metabolites of E. coli toward these 5 compounds, and we retained the set of 18’925 biologically viable pathways based on their bioenergetics feasibility and yields. For each novel reaction in the viable pathways, we proposed the most similar KEGG reactions and their gene sequences as candidates for either a direct experimental implementation or enzyme engineering. Furthermore, we classified feasible pathways depending on the reactions and precursors that were essential for production of the target molecules. This study shows the potential of BNICE.ch for future synthetic biology and metabolic engineering studies.