Abstract: The present invention relates to a nucleic acid molecule encoding a fusion protein comprising a secretion signal comprising (i) a signal peptide sequence originating from a KRE1 protein or a signal peptide sequence originating from a SWP1 protein; and optionally (ii) an ?-mating factor (MF?) pro-sequence, and a protein of interest. The present invention further relates to a secretion signal as defined herein, an expression cassette comprising said nucleic acid molecule as well as recombinant eukaryotic host cells comprising said nucleic acid molecule or expression cassette. Further encompassed is a method of manufacturing a protein of interest in a eukaryotic host cell and a method of increasing the secretion of a protein of interest from a eukaryotic host cell. Further provided is the use of the secretion signal for increasing the secretion of a recombinant protein of interest from a eukaryotic host cell and the use of the recombinant host cell for manufacturing a recombinant protein of interest.

Abstract: The present invention is in the field of recombinant biotechnology, in particular in the field of protein expression. The invention generally relates to a method of increasing the yield of a protein of interest (POI) in a eukaryotic host cell, preferably a yeast, by overexpressing at least one polynucleotide encoding at least one transcription factor of the present invention, preferably Msn4/2. The invention relates further to a recombinant eukaryotic host cell for manufacturing a POI, wherein the host cell is engineered to overexpress at least one polynucleotide encoding at least one transcription factor as well as the use of the host cell for manufacturing a POI.