Towards a penicilin producing yeast

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The research included in this thesis is aimed at further expanding the knowledge of using the yeast Hansenula plymorpha as alternative cell factory for the production of ß-lactam antibiotics. The rational behing this approach is the fact that yeast species have superior fermentation characteristics over filamentous fungi. Also, if successful, this approach will provide new opportunities for highly sustainable processes using cheap substrates and the development of generic strategies to produce modified ß-lactams and/or peptide antibiotics, using the highly advanced molecular and genetic toolbox that is available for H. polymorpha.
Initial studies revealed that introducing the P. chrysogenum penicillin biosynthetic pathway in yeast is paralleled by various fundamental problems of activation of these enzymes in the yeast host. Therefore we decided to follow a step by step strategy, introducing each component of the penicillin biosynthetic machinery individually in H. polymorpha and study their properties.

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