Non-noble　metal　single-atom　catalysts　hold　great　promise　in　selective　oxidation　reactions,　although　the　progress　is　still　unsatisfactory　because　of　the　synthesis　challenge　and　the　lack　of　mechanistic　interpretations.　Herein,　we　develop　a　biomolecule-based　strategy　to　synthesize　isolated　Co　single　atom　site　catalysts　by　one-step　pyrolysis　of　guanosine　and　Co　precursors.　Due　to　the　abundant　hydrogen　bonding　and　π-π　interaction　of　guanosine,　the　as-synthesized　Co-N-C　catalysts　present　a　hierarchical　porous　two-dimensional　(2D)　nanostructure　with　an　ultrahigh　specific　surface　area,　large　pore　volume,　and　high　density　of　cobalt　single　atoms.　Aberration-corrected　electron　microscopy　and　X-ray　photoelectron　spectroscopy　reveal　that　Co　species　are　present　as　isolated　single　sites　and　stabilized　by　nitrogen-doped　carbon　nanosheets.　These　characteristics　make　Co-GS-900　suitable　as　an　efficient　catalyst　for　selective　oxidation　of　aromatic　alkanes.　For　oxidation　of　ethylbenzene,　Co-GS-900　exhibits　a　superior　performancefwith　91%　conversion　and　98%　selectivity　of　acetophenone.　©　the　Owner　Societies　2021.