title: Regulation of alpha-aminoadipate reductase from Penicillium chrysogenum in relation to the flux from alpha-aminoadipate into penicillin biosynthesis.
abstract: The activity and regulation of alpha-aminoadipate reductase in three Penicillium chrysogenum strains (Q176, D6/1014/A, and P2), producing different amounts of penicillin, were studied. The enzyme exhibited decreasing affinity for alpha-aminoadipate with increasing capacity of the respective strain to produce penicillin. The enzyme from all three strains was inhibited by L-lysine, and the enzyme from the lowest producer, Q176, was least sensitive. Between pH 7.5 and 6.5, inhibition of alpha-aminoadipate reductase by L-lysine was pH dependent, being more pronounced at lower pH. The highest producer strain, P2, displayed the lowest alpha-aminoadipate reductase activity at pH 7.0. In Q176, the addition of 0.5-1 mM of exogenous lysine stimulated penicillin formation, whereas the same concentration was ineffective or inhibitory with strains D6/1014/A and P2. The addition of higher (up to 5 mM) lysine concentrations inhibited penicillin production in all three strains. In mutants of P. chrysogenum D6/1014/A, selected for resistance to 20 mM alpha-aminoadipate, highest penicillin production was observed in those strains whose alpha-aminoadipate reductase was most strongly inhibited by L-lysine. The results support the conclusion that the in vivo activity of alpha-aminoadipate reductase from superior penicillin producer strains of P. chrysogenum is more strongly inhibited by lysine, and that this is related to their ability to accumulate increased amounts of alpha-aminoadipate, and hence penicillin.
authors.affiliation: Abteilung für Mikrobielle Biochemie, Institut für Biochemische Technologie und Mikrobiologie, TU Wien, Austria.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: R L
authors.initials: RL
authors.lastname: Mach
authors.forename: K
authors.initials: K
authors.lastname: Affenzeller
authors.forename: C P
authors.initials: CP
authors.lastname: Kubicek
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase; D008239:Lysine / Q000494:pharmacology; D010403:Penicillin Resistance; D010406:Penicillins / Q000096:biosynthesis*; D010408:Penicillium chrysogenum / Q000201:enzymology*
chemical_list: D010406:Penicillins; D000445:Aldehyde Oxidoreductases; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase; D008239:Lysine