title: Simultaneous utilization of glucose and gluconate in Penicillium chrysogenum during overflow metabolism.
abstract: The filamentous fungus Penicillium chrysogenum is one of the most important production organism for β-lactam antibiotics, especially penicillin. A specific feature of P. chrysogenum is the formation of gluconate as the primary overflow metabolite under non-limiting growth on glucose. Gluconate can be formed extracellularly by the enzyme glucose oxidase (GOD) that shows high activities under glucose excess conditions. Currently, it is assumed that under these conditions glucose is the preferred carbon substrate for P. chrysogenum and gluconate consumption first starts after glucose becomes limiting. Here, we specifically address this hypothesis by combining batch cultivation experiments on defined glucose media, time-dependent GOD activity measurements, and (13)C-tracer studies. Our data prove that both substrates are metabolized simultaneously independent from the actual glucose concentration and therefore suggest that no distinct mechanism of carbon catabolite repression exists for gluconate in P. chrysogenum. Moreover, gluconate consumption does not interfere with penicillin V production by repression of the penicillin genes. Finally, by following a model-driven approach the specific uptake rates for glucose and gluconate were quantified and found to be significantly higher for gluconate. In summary, our results show that P. chrysogenum metabolizes gluconate directly and at high rates making it an interesting alternative carbon source for production purposes.
authors.affiliation: Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425, Jülich, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Schmitz
authors.forename: Vivien
authors.initials: V
authors.lastname: Peter
authors.forename: Sabine
authors.initials: S
authors.lastname: Meinert
authors.forename: Georg
authors.initials: G
authors.lastname: Kornfeld
authors.forename: Timo
authors.initials: T
authors.lastname: Hardiman
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wiechert
authors.forename: Stephan
authors.initials: S
authors.lastname: Noack
mesh_terms: D002244:Carbon / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D005942:Gluconates / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007553:Isotope Labeling; D053858:Metabolic Networks and Pathways; D010408:Penicillium chrysogenum / Q000378:metabolism*
chemical_list: D003470:Culture Media; D005942:Gluconates; D002244:Carbon; D005947:Glucose; C030691:gluconic acid
keywords: 13C-tracer; Penicillium chrysogenum; gluconate; overflow metabolism; penicillin