Post-translational enzyme modification by the phosphopantetheinyl transferase is required for lysine and penicillin biosynthesis but not for roquefortine or fatty acid formation in Penicillium chrysogenum

Carlos García-Estrada , Ricardo V. Ullán , Tania Velasco-Conde , Ramiro P. Godio , Fernando Teijeira , Inmaculada Vaca , Raúl Feltrer , Katarina Kosalková , Elba Mauriz , Juan F. Martín (1)

1 Molecular Biology

Nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) require a post-translational phosphopantetheinylation to become active. This reaction is catalysed by the 4'-phosphopantetheinyl transferase (PPTase). The ppt gene of Penicillium chrysogenum, encoding a protein that shares 50% homology with the stand-alone large PPTases, has been cloned. This gene is present as a single copy in the genome of the wild type and high penicillin producing strains (containing multiple copies of the penicillin gene cluster). Amplification of the ppt gene produced increases in isopenicillin N and benzylpenicillin biosynthesis. A PPTase defective mutant (Wis54-PPT—) was obtained. It required lysine and lacked pigment and penicillin production, but it still synthesized normal levels of roquefortine. The biosynthesis of roquefortine does not appear to involve a PPTase-mediated modification of the synthesizing enzymes. The PPT— mutant did not require fatty acids, which indicates that activation of the fatty acid synthase occurs by a different PPTase. Complementation of Wis54-PPT— with the ppt gene, restored lysine biosynthesis, pigmentation and penicillin production, which evidences the wide range of processes controlled by this gene.

Mots clés: Life Sciences

Carlos García-Estrada, Ricardo V. Ullán, Tania Velasco-Conde, Ramiro P. Godio, Fernando Teijeira, et al.. Post-translational enzyme modification by the phosphopantetheinyl transferase is required for lysine and penicillin biosynthesis but not for roquefortine or fatty acid formation in Penicillium chrysogenum. Biochemical Journal, 2008, 415 (2), pp.317-324. ⟨10.1042/BJ20080369⟩. ⟨hal-00478979⟩