Random mutagenesis and screening of complex glycoproteins: expression of human gonadotropins in Dictyostelium discoideum

The soil amoeba Dictyostelium discoideum is a host cell that provides simpl e genetics in combination with complex protein synthesis. We show that the complex human heterodimeric gonadotropins can be produced and secreted by t his organism, Furthermore, both follicle stimulation hormone and choriogona dotropin produced by D. dictyostelium bind to their human receptors and eli cit a biological response comparable to the wild-type hormones, We also sho w that structure-function analysis using random mutagenesis and screening o f recombinant glycoprotein hormones is feasible. Thus, expression of gonado tropins in D. dictyostelium opens the way to the engineering of potential n ew therapeutic analogues.