We show that a protein with no intrinsic inorganic synthesis activity can be endowed with the ability to control the formation of inorganic nanostructures under thermodynamically unfavorable (nonequilibrium) conditions, reproducing a key feature of biological hard-tissue growth and assembly. The nonequilibrium synthesis Of Cu2O nanoparticles is accomplished using an engineered derivative of the DNA-binding protein Tral in a room-temperature precursor electrolyte. The functional Tral derivative (Trali1753::CN225) is engineered to possess a cysteine-constrained 12-residue Cu2O binding sequence, designated CN225, that is inserted into a permissive site in Tral. When Trali1753::CN225 is included in the precursor electrolyte, stable Cu2O nanoparticles form, even though the concentrations of [Cu+] and [OH-] are at 5% of the solubility product (K-sp,K-Cu2O). Negative control experiments verify that Cu2O formation is controlled by inclusion of the CN225 binding sequence. Transmission electron microscopy and electron diffraction reveal a core-shell structure for the nonequilibrium nanoparticles: a 2 nm Cu2O core is surrounded by an adsorbed protein shell. Quantitative protein adsorption studies show that the unexpected stability Of Cu2O is imparted by the nanomolar surface binding affinity of Trali1753::CN225 for Cu2O (K-d = 1.2 x 10(-8) M), which provides favorable interfacial energetics (-45 kJ/mol) for the core-shell configuration. The protein shell retains the DNA-binding traits of Tral, as evidenced by the spontaneous organization of nanoparticles onto circular double-stranded DNA.