MODIFIED MUTEIN OF ERYTHROPOIETIN DERIVED FROM IN VITRO OR IN VIVO EXPRESSION SYSTEM ORIGINATED FROM MICROORGANISM AND METHOD FOR PRODUCING THE SAME

摘要

PROBLEM TO BE SOLVED: To provide a modified mutein of erythropoietin(EPO) with increased biological activity derived from in vitro or in vivo expression system of microorganism, and to provide a method for producing the same. SOLUTION: This method of producing the biologically active modified mutein of erythropoietin(EPO) comprises a process for converting the codon corresponding to amino acid residue at the site to be modified to an frameshift codon by site-directed mutagenesis; a process for preparing a mutein of EPO, during cell-free protein synthesis, by including a suppressor tRNA corresponding to the frame-shift codon to attach an unnatural amino acid attached to tRNA to EPO protein; and a process for incorporating a modifier(s) on the mutein of EPO. And the modified mutein of EPO obtained by the method.