Biosynthesis of Antifungal Solanimycin May Involve an Iterative Nonribosomal Peptide Synthetase Module

Dickeya solani, a plant-pathogenic bacterium, produces solanimycin, a potent hybrid polyketide/nonribosomal peptide (PKS/ NRPS) anti-fungal compound. The biosynthetic gene cluster responsible for synthesis of this compound has been identified. Because of instability, the complete structure of the compound has not yet been elucidated, but LC-MS2 identified that the cluster produces two main compounds, solanimycin A and B, differing by a single hydroxyl group. The fragmentation pattern revealed that the central part of solanimycin A is a hexapeptide, Gly-Dha-Dha-Dha-Dha-Dha (where Dha is dehydroalanine). This is supported by isotopic labeling studies using labeled serine and glycine. The N-terminal group is a polyketide-derived C16 acyl group containing a conjugated hexaene, a hydroxyl, and an amino group. The additional hydroxyl group in solanimycin B is on the alpha-carbon of the glycine residue. The incorporation of five sequential Dha residues is unprecedented because there is only one NRPS module in the cluster that is predicted to activate and attach serine (which is subsequently dehydrated to Dha), meaning that this NRPS module must act iteratively. While a few other iterative NRPS modules are known, they all involve iteration of two or three modules. We believe that the repetitive use of a single module makes the solanimycin biosynthetic pathway unique among NRPSs so far reported.

Automated summary

Dickeya solani, a pathogenic bacterium, produces a potent anti-fungal compound called solanimycin. The biosynthetic gene cluster responsible for its synthesis has been identified, and LC-MS2 analysis revealed the presence of two main compounds, solanimycin A and B. The structure of solanimycin A was found to be a hexapeptide and it is the first reported example of a nonribosomal peptide (NRPS) module acting iteratively. This unique pathway makes solanimycin biosynthesis distinct from other NRPSs.