Improving fungal cell factories: implementing lessons from fungal ageing models
Zusammenfassung der Projektergebnisse
Identification and characterization of novel genes involved in constitutive peroxisome degradation: Peroxisomes are essential organelles in mammals. They are important for performing various biochemical functions, like degradation of very long chain fatty acids. Peroxisomes are subject to dysfunction as time progresses. Dysfunctional organelles are degraded by the cell via autophagy (pexophagy) to prevent further damage and to recycle valuable components. New peroxisomes are formed either by fission of existing (most likely undamaged) ones or by formation from the endoplasmic reticulum (de novo pathway). It is not well understood how damaged peroxisomes are recognized by the autophagy (pexophagy) machinery. In order to gain insight into this process, the yeast Hansenula polymorpha was used to study pexophagy and to identify new genes that mediate this process. Two promising genes were identified after screening a library of mutants. Further work is needed to validate these candidates as hitherto unknown factors controlling constitutive pexophagy. Improving fungal cell factories: implementing lessons from fungal ageing models: By overproduction of glyoxalase enzymes that mediate the degradation of a toxic metabolic by-product, methylglyoxal, it was possible to improve one of the main producers of antibiotics, the fungus Penicillium chrysogenum. The levels of two proteins involved in the biosynthesis of penicillin are significantly increased, most likely by prevention of damage by methylglyoxal and related compounds. Indeed, we could show that cellular extracts prepared from transformants overexpressing glyoxalase genes contain a reduced amount of methylglyoxal-modified proteins. Glyoxalase transformants are capable to produce more penicillin than the control strain, especially at elevated growth temperatures. This is highly relevant for industrial purposes. Taken together, we could demonstrate that overproduction of glyoxalases is a novel way to improve the biosynthetic performance of a fungus used in industry. Moreover, our findings can be relatively easy transferred to other fungal organisms and other production strategies. Therefore, the results are not limited to the production of antibiotics but, in theory, also applicable to production of other valuable compounds synthesized by unicellular and filamentous fungi (e. g., antigens, organic acids, anticholesterol statins, immunosuppressantants (cyclosporins), steroids, bioethanol, etc.).
Projektbezogene Publikationen (Auswahl)
- 2012: The impact of peroxisomes on cellular aging and death. Front Oncol 2:50
Manivannan S, Scheckhuber CQ, Veenhuis M, van der Klei IJ
- 2013: Improving penicillin biosynthesis in Penicillium chrysogenum by glyoxalase overproduction. Metab Eng
Scheckhuber CQ, Veenhuis M, van der Klei IJ
(Siehe online unter https://doi.org/10.1016/j.ymben.2013.04.003)
