NADPH-dependent glutamate dehydrogenase in Penicillium chrysogenum is involved in regulation of β-lactam production

摘要

The interactions between the ammonium assimilatory pathways and β-lactam production were investigated by disruption of the NADPH-dependent glutamate dehydrogenase gene (gdhA) in two industrial β-lactam-producing strains of Penicillium chrysogenum. The strains used were an adipoyl-7-ADCA- and a penicillin-producing strain. The gdhA gene disruption caused a decrease in maximum specific growth rate of 26?% and 35?% for the adipoyl-7-ADCA-producing strain and the penicillin-producing strain, respectively, compared to the corresponding reference strains. Interestingly, no β-lactam production was detected in either of the ΔgdhA strains. Supplementation with glutamate restored growth but no β-lactam production was detected for the constructed strains. Cultures with high ammonium concentrations (repressing conditions) and with proline as nitrogen source (de-repressed conditions) showed continued β-lactam production for the reference strains whereas the ΔgdhA strains remained non-productive under all conditions. By overexpressing the NAD-dependent glutamate dehydrogenase, the specific growth rate could be restored, but still no β-lactam production was detected. The results indicate that the NADPH-dependent glutamate dehydrogenase may be directly or indirectly involved in the regulation of β-lactam production in industrial strains of P. chrysogenum.