HOST CELLS AND METHODS OF USE

摘要

The present invention provides genetically modified Pichia strains wherein at least one nucleic acid sequence encoding a functional gene product and/or at least one nucleic acid sequence necessary for expression of at least one functional gene product in said Pichia strain is genetically modified, wherein said gene product is responsible for proteolysis and/or glycosylation in said genetically modified Pichia strain. In particular, Pichia strains are provided wherein nucleic acid sequence encoding a functional gene product or expression of said gene product are genetically modified: PEP4, PRB1, YPS1 , YPS2 , YMP1 , YMP2, YMP3 and PMT4. Also provided herein are genetically modified host cells wherein wild type parent of said genetically modified host cell comprises a gene encoding a polypeptide having at least 60% sequence identity to amino acids 1-865 of SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8wherein said gene is genetically modified in the genome of said host cell such that the gene product is reduced or eliminated in said genetically modified host cell compared with said wild type host cell.