Transgene S.a.

Martine Nguyen

Tilman Achstetter

Yves Lemoine

Jean-Marc Reichhart

The present invention relates to an improved system for producing mature heterologous proteins, and especially hirudin, by means of yeasts comprising an expression vector containing a sequence coding for the heterologous protein. This improvement is characterized by amplification of the KEX2 gene of yeast, coding for the endoprotease yscF. The amplification is carried out either by integration of one or more copies of all or part of the KEX2 gene in the yeast genome, or by insertion of one or more copies of all or part of the KEX2 gene into the vector for expression of the heterologous protein.

Yeast strains for the production of mature heterologous proteins,

The invention relates to new DNA fragments and to their application as a DNA coding fragment for a signal peptide which can be used for the secretion of proteins, said peptide including a sequence of amino-acids which show a degree of correspondence of at least 60% with the sequence of amino-acids (I) or (II), preferably with the sequence (II). The sequences (I) and (II) are as follows: (I) Arg-Phe-Ser-Thr-Thr-Leu-Ala-Thr-Ala-Ala-Thr-Ala-Leu-Phe-Phe-Thr-Ala-Ser-Gl n. (II) Arg-Phe-Ser-Thr-Thr-Leu-Ala-Thr-Ala-Ala-Thr-Ala-Leu-Phe-Phe-Thr-Ala-Ser-Gl n-Val-Ser-Ala.

Application of novel DNA fragments as a coding sequence for a signal

Yeast vector coding for heterologous gene fusions linked via KEX2

The invention relates to a new strain of Saccharomyces cerevisiae productive of a heterologous protein, and more especially of hirudin, characterized by a suppression of the proteolytic function encoded by the PRC1 gene. More specifically, this deficiency is due to a mutation or more especially to a deletion of the PRC1 structural gene.

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Wittersheim, France

Martine Nguyen