Abstract

170
Annabel C. Murphy, Matthew Corney, Rita E. Monson, Miguel A. Matilla, George P. C. Salmond and Finian J. Leeper
"Biosynthesis of Antifungal Solanimycin May Involve an Iterative Non-Ribosomal Peptide Synthetase (NRPS) Module"
ACS Chem. Biol., 2023, 18 (5), 1148–1157. Full text

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 labelling studies using labelled 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 a-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 the repetitive use of a single module makes the solanimycin biosynthetic pathway unique amongst NRPSs so far reported.

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