Biosynthesis of syringomycin: mutational analysis of the genes syrB1, syrB2 and syrC.

The biosynthetic cluster of the antifungal lipodepsipeptide syringomycin (SR) produced by Pseudomonas syringae is a prototype of the non linear type of the Nonribosomal Peptide Synthetases.It is organized in three transcriptional units: syrB1/B2, syrC and syrE. SyrE encodes a multimodular peptide synthetase and syrB1 is relative to a didomain module involved in the activation of threonine, the biosynthetic precursor of 4-chlorothreonine SyrB2 and SyrC encode a Fe-nonheme dependent enzyme and an α,β-hydrolase, respectively. Both are shown to indispensable in the biosynthesis of SR, and the residues important for their activity were shown by site-directed mutagenesis and in trans complementation experiments of Pseudomonas syringae mutant strains inactivated in either syrB2 or syrC genes. The apo-SyrB2 was shown to bind Cu++. SyrB2 interacts with SyrB1, as shown by protein-protein interaction studies where anti SyrB2 antibodies were used.