title: delta-(L-alpha-Aminoadipyl)-L-cysteinyl-D-valine synthetase, that mediates the first committed step in penicillin biosynthesis, is a cytosolic enzyme.
abstract: Penicillin biosynthesis by Penicillium chrysogenum is a compartmentalized process. The first catalytic step is mediated by delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACV synthetase), a high molecular mass enzyme that condenses the amino acids L-alpha-aminoadipate, L-cysteine, and L-valine into the tripeptide ACV. ACV synthetase has previously been localized to the vacuole where it is thought to utilize amino acids from the vacuolar pools. We localized ACV synthetase by subcellular fractionation and immuno-electron microscopy under conditions that prevented proteolysis and found it to co-localize with isopenicillin N synthetase in the cytosol, while acyltransferase localizes in microbodies. These data imply that the key enzymatic steps in penicillin biosynthesis are confined to only two compartments, i.e., the cytosol and microbody.
authors.affiliation: Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.
authors.forename: Ted R
authors.initials: TR
authors.lastname: van der Lende
authors.forename: Mart
authors.initials: M
authors.lastname: van de Kamp
authors.forename: Marco
authors.initials: M
authors.lastname: Berg
authors.forename: Klaas
authors.initials: K
authors.lastname: Sjollema
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
authors.forename: Marten
authors.initials: M
authors.lastname: Veenhuis
authors.forename: Wil N
authors.initials: WN
authors.lastname: Konings
authors.forename: Arnold J M
authors.initials: AJ
authors.lastname: Driessen
mesh_terms: D003600:Cytosol / Q000201:enzymology*; D004795:Enzyme Stability; D008830:Microbodies; D008854:Microscopy, Electron; D010406:Penicillins / Q000096:biosynthesis*; D010408:Penicillium chrysogenum / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D010453:Peptide Synthases / Q000302:isolation & purification / Q000378:metabolism*; D011523:Protoplasts / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: D010406:Penicillins; D010453:Peptide Synthases; C095368:alpha-aminoadipyl-cysteinyl-valine synthetase