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

Area of Science:

• Microbiology
• Biochemistry
• Natural Products Chemistry

Background:

• *Dickeya solani* is a plant pathogen known to produce bioactive compounds.
• Solanimycin is a potent antifungal agent with a hybrid polyketide/nonribosomal peptide (PKS/NRPS) structure.
• The biosynthetic pathway of solanimycin was previously uncharacterized.

Purpose of the Study:

• To identify and characterize the biosynthetic gene cluster for solanimycin production in *Dickeya solani*.
• To elucidate the structural features and biosynthetic mechanism of solanimycin A and B.
• To investigate the unique iterative mechanism of the nonribosomal peptide synthetase (NRPS) module involved.

Main Methods:

• Identification of the solanimycin biosynthetic gene cluster.
• Liquid chromatography-tandem mass spectrometry (LC-MS²) for structural analysis.
• Isotopic labeling studies using labeled serine and glycine.

Main Results:

• The gene cluster responsible for solanimycin biosynthesis was identified.
• Solanimycin A and B were identified, differing by a single hydroxyl group.
• The central hexapeptide core of solanimycin A consists of five sequential dehydroalanine (Dha) residues, derived from serine.
• A single NRPS module iteratively activates and dehydrates serine to form the Dha residues.

Conclusions:

• The solanimycin biosynthetic pathway utilizes a unique iterative mechanism involving a single NRPS module.
• This iterative PKS/NRPS pathway is unprecedented in known NRPS systems.
• Understanding this pathway offers insights into novel natural product biosynthesis and enzyme mechanisms.