title: Cytosolic NADPH metabolism in penicillin-G producing and non-producing chemostat cultures of Penicillium chrysogenum.
abstract: This study addresses the relation between NADPH supply and penicillin synthesis, by comparing the flux through the oxidative branch of the pentose phosphate pathway (PPP; the main source of cytosolic NADPH) in penicillin-G producing and non-producing chemostat cultures of Penicillium chrysogenum. The fluxes through the oxidative part of the PPP were determined using the recently introduced gluconate-tracer method. Significantly higher oxidative PPP fluxes were observed in penicillin-G producing chemostat cultures, indicating that penicillin production puts a major burden on the supply of cytosolic NADPH. To our knowledge this is the first time direct experimental proof is presented for the causal relationship between penicillin production and NADPH supply. Additional insight in the metabolism of P. chrysogenum was obtained by comparing the PPP fluxes from the gluconate-tracer experiment to oxidative PPP fluxes derived via metabolic flux analysis, using different assumptions for the stoichiometry of NADPH consumption and production.
authors.affiliation: Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands.
authors.forename: Roelco J
authors.initials: RJ
authors.lastname: Kleijn
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Wouter A
authors.initials: WA
authors.lastname: van Winden
authors.forename: Walter M
authors.initials: WM
authors.lastname: van Gulik
authors.forename: Cor
authors.initials: C
authors.lastname: Ras
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Heijnen
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010400:Penicillin G / Q000378:metabolism*; D010408:Penicillium chrysogenum / Q000378:metabolism*; D010427:Pentose Phosphate Pathway
chemical_list: D000900:Anti-Bacterial Agents; D009249:NADP; D010400:Penicillin G