GENETICALLY ENGINEERED YEAST WITH MODIFIED SIGNAL PEPTIDASE COMPLEX

摘要

The present invention provides a yeast cell comprising a nucleic acid functionally encoding a eukaryotic (e.g., mammalian) protein homologue of a subunit (Sec11p, Spc1p, Spc2p and/or Spc3p) of the yeast signal peptidase complex. The yeast cell of this invention can be, for example, of the genus Saccharomyces, Schizosaccharomyces, Pichia, Hansenula, Kluyveromyces and/or Yarrowia. Furthermore, the yeast cell can lack one or more functional subunits (Sec11p, Spc1p, Spc2p and/or Spc3p) of the yeast signal peptidase complex. The present invention further provides a method for producing a protein heterologous to a yeast cell comprising expressing, in the yeast cell of this invention, a nucleic acid functionally encoding the heterologous protein under conditions which permit the expression of the nucleic acid as a precursor protein having a signal peptide and processing of the precursor protein to a signal peptide-cleaved form of the protein. A method is also provided for obtaining increased production of a protein heterologous to a yeast cell comprising expressing, in the yeast cell of this invention, a nucleic acid functionally encoding the heterologous protein under conditions which permit the expression of the nucleic acid as a precursor protein having a signal peptide and processing of the precursor protein to a signal peptide-cleaved form of the protein. Additionally provided is a method for producing a yeast cell capable of increased production of a protein heterologous to the yeast cell, comprising introducing into the yeast cell (with or without one or more functional SPC subunits) a nucleic acid which functionally encodes one or more eukaryotic protein homologues of the signal peptidase complex under conditions permitting the expression of the nucleic acid as the protein homologues.