Overproduction of a single protein, Pc-Pex11p, results in 2-fold enhanced penicillin production by Penicillium chrysogenum

• Published in: Fungal genetics and biology 2005-02, Vol.42 (2), p.154-164
• Main Authors: Kiel, Jan A.K.W., van der Klei, Ida J., van den Berg, Marco A., Bovenberg, Roel A.L., Veenhuis, Marten
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Anti-Bacterial Agents - biosynthesis; Antibiotics; biosynthesis; complementary DNA; Filamentous fungi; fungal proteins; Fungal Proteins - biosynthesis; Fungal Proteins - genetics; Gene Dosage; Gene Expression Regulation, Fungal; gene overexpression; genes; Genes, Fungal - genetics; Genes, Fungal - physiology; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Methylotrophic yeast; Microbodies; Microbodies - genetics; Microbodies - metabolism; Microbodies - ultrastructure; Molecular Sequence Data; penicillins; Penicillins - biosynthesis; Penicillium chrysogenum; Penicillium chrysogenum - genetics; Penicillium chrysogenum - metabolism; Penicillium chrysogenum - ultrastructure; PEX gene; Transcriptional Activation; β-Lactam
• ISSN: 1087-1845; 1096-0937
• DOI: 10.1016/j.fgb.2004.10.010

Current industrial production of β-lactam antibiotics, using the filamentous fungus Penicillium chrysogenum, is the result of many years of strain improvement by classical mutagenesis. More efficient production strains showed significant increases in the number and volume fraction of microbodies in their cells, organelles that harbor key enzymes involved in the biosynthesis of β-lactam antibiotics. We have isolated the P. chrysogenum cDNA encoding Pc-Pex11p, a peroxin that is involved in microbody abundance. We demonstrate that overproduction of Pc-Pex11p in P. chrysogenum results in massive proliferation of tubular-shaped microbodies and a 2- to 2.5-fold increase in the level of penicillin in the culture medium. Notably, Pc-Pex11p-overproduction did not affect the levels of the enzymes of the penicillin biosynthetic pathway. Our results suggest that the stimulating effect of enhanced organelle numbers may reflect an increase in the fluxes of penicillin and/or its precursors across the now much enlarged microbody membrane.