title: Peroxisomes are required for efficient penicillin biosynthesis in Penicillium chrysogenum.
abstract: In the fungus Penicillium chrysogenum, penicillin (PEN) production is compartmentalized in the cytosol and in peroxisomes. Here we show that intact peroxisomes that contain the two final enzymes of PEN biosynthesis, acyl coenzyme A (CoA):6-amino penicillanic acid acyltransferase (AT) as well as the side-chain precursor activation enzyme phenylacetyl CoA ligase (PCL), are crucial for efficient PEN synthesis. Moreover, increasing PEN titers are associated with increasing peroxisome numbers. However, not all conditions that result in enhanced peroxisome numbers simultaneously stimulate PEN production. We find that conditions that lead to peroxisome proliferation but simultaneously interfere with the normal physiology of the cell may be detrimental to antibiotic production. We furthermore show that peroxisomes develop in germinating conidiospores from reticule-like structures. During subsequent hyphal growth, peroxisome proliferation occurs at the tip of the growing hyphae, after which the organelles are distributed over newly formed subapical cells. We observed that the organelle proliferation machinery requires the dynamin-like protein Dnm1.
authors.affiliation: Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kluyver Centre for Genomics of Industrial Fermentation, P.O. Box 14, 9750 AA Haren, The Netherlands.
authors.forename: Wiebe H
authors.initials: WH
authors.lastname: Meijer
authors.forename: Loknath
authors.initials: L
authors.lastname: Gidijala
authors.forename: Susan
authors.initials: S
authors.lastname: Fekken
authors.forename: Jan A K W
authors.initials: JA
authors.lastname: Kiel
authors.forename: Marco A
authors.initials: MA
authors.lastname: van den Berg
authors.forename: Romeo
authors.initials: R
authors.lastname: Lascaris
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
authors.forename: Ida J
authors.initials: IJ
authors.lastname: van der Klei
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D034284:Dynamin I / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D025301:Hyphae / Q000201:enzymology / Q000254:growth & development / Q000648:ultrastructure; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D010406:Penicillins / Q000096:biosynthesis*; D010408:Penicillium chrysogenum / Q000201:enzymology / Q000378:metabolism*; D020675:Peroxisomes / Q000201:enzymology / Q000378:metabolism*; D013172:Spores, Fungal / Q000201:enzymology / Q000648:ultrastructure
chemical_list: D005656:Fungal Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D000217:Acyltransferases; C018756:acyl-CoA-6-aminopenicillanic acid acyltransferase; D034284:Dynamin I; D003066:Coenzyme A Ligases; C023914:phenylacetate - CoA ligase