Synthesis and Secretion of Mammalian Proteins in Yeast

Various types of yeast expression vectors were constructed containing regulatory sequences of different yeast genes. Human growth hormone (hGH) gene expression was studied under the control of promoters and secretion signal sequences of yeast PHO5 and MFal genes. Using different gene constructions, including mature hGH genes, pre-hGH genes with homologous or heterologous secretion signal sequences, we investigated the influence of structural changes in the 5′-nontranslated region and in the secretion signal sequence on hGH synthesis, processing and export in yeast. Yeast cells recognised and cleaved off correctly the mammalian (hGH) secretion signal sequence and 10%–20% of the hGH produced appeared in the medium in mature form. Promoter and ‘prosegment’ of MFal gene provided for more efficient synthesis and secretion of hGH, so that 65% of the protein made in yeast was exported to the culture medium.