Heterologous expression of a cryptic gene cluster from Marinomonas fungiae affords a novel tricyclic peptide marinomonasin

The omega-ester-containing peptides (OEPs) are a group of ribosomally synthesized and post-translationally modified peptides (RiPPs). The biosynthetic gene clusters of omega-ester-containing peptides commonly include ATP-grasp ligase coding genes and are distributed over the genomes of a wide variety of bacteria. A new biosynthetic gene cluster of omega-ester-containing peptides was found in the genome sequence of the marine proteobacterium Marinomonas fungiae. Heterologous production of a new tricyclic peptide named marinomonasin was accomplished using the biosynthetic gene cluster in Escherichia coli expression host strain BL21(DE3). By ESI-MS and NMR experiments, the structure of marinomonasin was determined to be a tricyclic peptide 18 amino acids in length with one ester and two isopeptide bonds in the molecule. The bridging patterns of the three intramolecular bonds were determined by the interpretation of HMBC and NOESY data. The bridging pattern of marinomonasin was unprecedented in the omega-ester-containing peptide group. The results indicated that the ATP-grasp ligase for the production of marinomonasin was a novel enzyme possessing bifunctional activity to form one ester and two isopeptide bonds.

Automated summary

Omega-ester-containing peptides are ribosomally synthesized and post-translationally modified peptides commonly including ATP-grasp ligase coding genes, found in various bacteria. A new biosynthetic gene cluster for omega-ester-containing peptides was discovered in Marinomonas fungiae, leading to successful heterologous production of a new tricyclic peptide called marinomonasin in Escherichia coli. The structure of marinomonasin was determined to be unique in the omega-ester-containing peptide group, with an unprecedented bridging pattern of intramolecular bonds.