Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalysis are required in metal-air batteries and an efficient dual-functional single-atom catalyst (SAC) is still lacking. This is partly because of the limited synthesis strategies to modify the coordination environment of metal centers in SACs. Herein, we report a genetic strategy, transformation from thiometallate anions in the precursor to metal-sulfur bonding in carbon, producing hollow-sphere-structured Mo SAC with O/N/S co-coordination as an efficient ORR/OER dual-functional catalyst. The MoS42−-doped polydopamine have O/S co-coordination for Mo, which converts into S/O/N co-coordination in carbon during pyrolysis. We established that coordination engineering, specifically S coordination, could boost the ORR catalysis of Mo SAC. The low ORR half-wave potential (E1/2) and small Tafel slope are among the best of Mo-based non-noble metal catalysts. The OER overpotential of 303 mV at 10 mA cm−2 is significantly lower than that of commercial IrO2, and Pt/C. Assembled Zn-air batteries can work steadily for 90 h without significant voltage decay. Our strategy can be extended to the synthesis of other group-V and group-VI metal hollow SACs with an S coordination, such as W.