title: Impact of the cross-pathway control on the regulation of lysine and penicillin biosynthesis in Aspergillus nidulans.
abstract: The non-proteinogenic amino acid, alpha-aminoadipate, defines the biosynthetic branch-point of lysine and penicillin biosynthesis in the filamentous fungus, Aspergillus nidulans. Regulation of both pathways was analysed in response to amino acid limitation. The lysF-encoded homoaconitase acts upstream of the alpha-aminoadipate branch point, whereas the lysA gene product, saccharopine dehydrogenase, catalyses the ultimate step of the lysine-specific branch. The lysA gene from A. nidulans was identified and isolated. Amino acid starvation resulted in significantly increased transcription of lysA but not lysF. Starvation-dependent changes in transcription levels of lysA were dependent on the presence of the central transcriptional activator of the cross-pathway control (CPCA). The effect of amino acid starvation under penicillin-producing conditions was analysed in A. nidulans strains with reporter genes for the penicillin-biosynthesis genes, acvA and ipnA, and genetically altered activity of the cross-pathway control. Overproduction of CPCA decreased expression of ipnAand acvA reporter genes and even more drastically reduced penicillin production. This work suggests that, upon amino acid starvation, the cross-pathway control overrules secondary metabolite biosynthesis and favours the metabolic flux towards amino acids instead of penicillin in A. nidulans.
authors.affiliation: Institut für Mikrobiologie und Genetik, Georg-August-Universität, Grisebachstrasse 8, 37077 Göttingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Busch
authors.forename: Helge B
authors.initials: HB
authors.lastname: Bode
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Braus
mesh_terms: D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010406:Penicillins / Q000096:biosynthesis*; D012443:Saccharopine Dehydrogenases / Q000235:genetics; D020539:Sequence Analysis, Protein; D017385:Sequence Homology
chemical_list: D001426:Bacterial Proteins; D010406:Penicillins; D012443:Saccharopine Dehydrogenases; C029496:saccharopine dehydrogenase (NADP+, lysine-forming); D002262:Carboxy-Lyases; C079912:LysA protein, Bacteria; D008239:Lysine