Overproduction of a single protein, Pc-Pex11p, results in 2-fold enhanced penicillin production by Penicillium chrysogenum.
Current industrial production of beta-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 beta-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.
Kiel
Jan A K W
JA
Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, PO Box 14, NL-9750 AA Haren, The Netherlands. j.a.k.w.kiel@biol.rug.nl
van der Klei
Ida J
IJ
van den Berg
Marco A
MA
Bovenberg
Roel A L
RA
Veenhuis
Marten
M
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008830:Microbodies / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010406:Penicillins / Q000096:biosynthesis*; D010408:Penicillium chrysogenum / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015533:Transcriptional Activation
D000900:Anti-Bacterial Agents; D005656:Fungal Proteins; D008565:Membrane Proteins; D010406:Penicillins