Identification and analysis of genes from Streptomyces pristinaespiralis encoding enzymes involved in the biosynthesis of the 4-dimethylamino-L-phenylalanine precursor of pristinamycin I

Blanc V., Gil Patricia, Bamas-Jacques Nathalie, Lorenzon Sophie, Zagorec Monique, Schleuniger Josiane, Bisch Didier, Blanche Francis, Debussche Laurent, Crouzet Joël, Thibaut Denis. 1997. Identification and analysis of genes from Streptomyces pristinaespiralis encoding enzymes involved in the biosynthesis of the 4-dimethylamino-L-phenylalanine precursor of pristinamycin I. Molecular Microbiology, 23 (2) : 191-202.

https://doi.org/10.1046/j.1365-2958.1997.2031574.x

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Résumé : Four pap genes (papA, papB, papC, papM) were found by sequencing near to snbA, a Streptomyces pristinaespiralis gene which was previously shown to encode one of the pristinamycin I (PI) synthetases. Analysis of the homologies observed from the deduced amino acid sequences suggested that these four genes could be involved in the biosynthesis of the PI precursor 4-dimethylamino-L-phenylalanine (DMPAPA). This was first verified when disruption of papA in S. pristinaespiralis led to a Pl- phenotype, which was reversed by the addition of DMPAPA into the culture medium. Further confirmation was obtained when papM was overexpressed in Escherichia coli and the corresponding protein purified to homogeneity. It catalysed the two successive N-methylation steps of 4-amino-L-phenylalanine leading to DMPAPA via 4-methylamino-L-phenylalanine. These results allowed us to assign a function to each of the four pap genes and to propose a biosynthetic pathway for DMPAPA.

Mots-clés Agrovoc : séquence nucléotidique, Streptomyces, enzyme, antibiotique, acide aminé

Mots-clés complémentaires : Séquencage

Classification Agris : L50 - Physiologie et biochimie animales

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