High Institute of Medical Technologies of Tunis

Title: Bioprocessing in the dimorphic yeast Yarrowia lipolytica and Biopharmaceutical marketing: Progress and challenges


Saoussen Turki has completed her PhD in Microbiology from the Pasteur Institute of Tunis in 2010. First, she carried out a Master project with the aim to develop a bioprocess for the production of human interferon alpha by high-cell density culture of Pichia pastoris. Then, she worked in collaboration with Wallon Center of Industrial Biology in Belgium to study the potential of the yeast Yarrowia lipolytica to produce a lipase of pharmaceutical grade. She has published 5 papers in international journals and one chapter book. Since 2008, she was appointed as a Teaching associate at High Institute of Medical Technologies of Tunis to develop a Microbiology engineering teaching program for Medical Biotechnology undergraduates.


In the two last decades, Yarrowia lipolytica has emerged as one of the most promising host system for the production of therapeutic proteins. For the few last years, many processes have been developed to produce native and recombinant proteins of medical interest. A great attention has been paid to the molecular aspects of homologous/heterologous gene expression in Yarrowia lipolytica. A wide range of strain engineering approaches and molecular tools have been applied to deal with multiple factors affecting the yield and the quality of the therapeutic product expressed in this oleaginous yeast. It resulted in a successful development of powerful strains with various characteristics such as higher protein production and secretion capacity, enhanced processing and folding potential or humanized glycosylation pattern. However, for large-scale production, opportunities and limitations related to fermentation technology have also to be considered. The knowledge of fermentation techniques for this yeast is being accumulated over the last years with a noticeable progress in culture media optimization and process design and development. The prospect of cost-competitive production of human medicines in Yarrowia lipolytica is actually being closer than ever before, but, its future is challenging yet. Issues related to cell morphology changes during culture, heterogeneity of the culture media due to the presence of oily non soluble substrates and proteases endogenous activity of the yeast are yet uncontrolled parameters. They may impact the processes consistency and productivity and limit the commercialization of Yarrowia lipolytica –derived therapeutics. These issues need to be addressed before the dimorphic yeast becomes an acceptable mainstream production technology.