Abstract: An enzyme capable of reducing the antibiotic activity (i.e., toxicity) of streptothricin with respect to eukaryotic cells without sacrificing antibiotic activity with respect to prokaryotic cells is provided along with a streptothricin derivative having reduced toxicity with respect to eukaryotic cells while retaining antibiotic activity with respect to prokaryotic cells, and a manufacturing method thereof. By opening the lactam ring of streptothricin, a protein having the amino acid sequence according to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14 or 16 of the invention can reduce the antibiotic activity of streptothricin D with respect to eukaryotic cells without sacrificing antibiotic activity with respect to prokaryotic cells.