%0 Journal Article %A Teves, Franco %A Lamas-Maceiras, Mónica %A García-Estrada, Carlos %A Casqueiro, Javier %A Naranjo, Leopoldo %A Ullán, Ricardo V. %A Scervino, José-Martín %A Wu, Xiaobin %A Velasco-Conde, Tania %A Martín, Juan F. %T Transcriptional upregulation of four genes of the lysine biosynthetic pathway by homocitrate accumulation in Penicillium chrysogenum: homocitrate as a sensor of lysine-pathway distress %D 2009 %J Microbiology, %V 155 %N 12 %P 3881-3892 %@ 1465-2080 %R https://doi.org/10.1099/mic.0.031005-0 %K IRP, iron regulatory protein %I Microbiology Society, %X The lysine biosynthetic pathway has to supply large amounts of α-aminoadipic acid for penicillin biosynthesis in Penicillium chrysogenum. In this study, we have characterized the P. chrysogenum L2 mutant, a lysine auxotroph that shows highly increased expression of several lysine biosynthesis genes (lys1, lys2, lys3, lys7). The L2 mutant was found to be deficient in homoaconitase activity since it was complemented by the Aspergillus nidulans lysF gene. We have cloned a gene (named lys3) that complements the L2 mutation by transformation with a P. chrysogenum genomic library, constructed in an autonomous replicating plasmid. The lys3-encoded protein showed high identity to homoaconitases. In addition, we cloned the mutant lys3 allele from the L2 strain that showed a G1534 to A1534 point mutation resulting in a Gly495 to Asp495 substitution. This mutation is located in a highly conserved region adjacent to two of the three cysteine residues that act as ligands to bind the iron–sulfur cluster required for homoaconitase activity. The L2 mutant accumulates homocitrate. Deletion of the lys1 gene (homocitrate synthase) in the L2 strain prevented homocitrate accumulation and reverted expression levels of the four lysine biosynthesis genes tested to those of the parental prototrophic strain. Homocitrate accumulation seems to act as a sensor of lysine-pathway distress, triggering overexpression of four of the lysine biosynthesis genes. %U https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.031005-0