Effect of phenoxyacetic acid on the glutathione metabolism ofPenicillium chrysogenum

In the idiophase of penicillin V fermentations, the β-lactam biosynthetic machinery of Penicillium chrysogenum is subject to the inhibitory effect of glutathione (GSH) meanwhile the GSH-dependent activation of phenoxyacetic acid (POA) via the formation of (S-phenoxyacetyl)glutathione seems to be unlikely. Our experimental findings suggest that both the intracellular GSH concentrations and the redox capacity of the GSH/GSSG system overweigh the needs raised by the β-lactam production in well-controlled fed-batch penicillin V fermentations. That is, keeping the intracellular GSH levels low, e.g. by the construction of low GSH-producer P. chrysogenum strains, could be beneficial for the antibiotic production. Importantly, its exceptionally potent antioxidant defence system enables the micro-organism to prevent the intracellular accumulation of reactive oxygen species even at low intracellular GSH levels. As a protonophore which is transported across the plasma membrane solely by free diffusion, POA is toxic to P. chrysogenum and accumulates inside mycelia especially when the extracellular pH drops below 6.0. Nevertheless, P. chrysogenum cells eliminate POA quite efficiently most probably via a GSH-dependent pathway under these circumstances.