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Journal Article

Impact of the cross-pathway control on the regulation of lysine and penicillin biosynthesis in Aspergillus nidulans

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Busch, S., Bode, H. B., Brakhage, A., & Braus, G. (2003). Impact of the cross-pathway control on the regulation of lysine and penicillin biosynthesis in Aspergillus nidulans. CURRENT GENETICS, 42(4), 209-219. doi:10.1007/s00294-002-0333-8.

Cite as: https://hdl.handle.net/21.11116/0000-000A-093B-B
The non-proteinogenic amino acid, a-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 a-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 increase 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 ipnA and 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.