Peroxisome biosynthesis and function in Penicillium chrysogenum

PhD ceremony: Mr. W.H. Meijer, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen

Thesis: Peroxisome biosynthesis and function in Penicillium chrysogenum

Promotor(s): prof. M. Veenhuis, prof. I.J. van der Klei, prof. R.A.L. Bovenberg

Faculty: Mathematics and Natural Sciences

The antibiotic penicillin is produced on an industrial scale using the fungus Penicillium chrysogenum. The first two enzymatic reactions in the penicillin biosynthetic pathway are in the cytosol, the last in an organelle, the peroxisome. The research of Wieb Meijer has shown that peroxisomes are very important for the production of penicillin . He has shown that a correlation exists between the number of peroxisomes per cell and the amount of penicillin produced. Second, we have shown that defects in the formation of peroxisomes result in a reduced penicillin production.

Phenylacetic acid or phenoxyacetic acid are commonly used as a novel side chain in the industrial production of penicillin. Using microscopy Meijer has concluded that the enzyme responsible for the activation of phenylacetic acid and phenoxyacetic acid, Phenylacetyl CoA Ligase (PCL), is localized in peroxisomes. This enzyme is very important for penicillin production because a P. chrysogenum strain in which PCL was not produced showed a reduced penicillin production. This strain however still was capable of producing low concentrations of penicillin, which shows that besides PCL other enzyme(s) are capable of activating phenylacatic acid or phenoxyacitic acid are present in P. chrysogenum.

For the effective production of penicillin besides the peroxisomal enzyme content the peroxisomal stability is an equal important factor. To obtain more insight in genes that are possibly involved in peroxisomal degradation (autophagy) Meijer has performed a detailed in silico analaysis. From this research he concluded that the genes involved in autophagy are conserved in P. chrysogenum