JM47, a cyclic tetrapeptide HC-toxin analogue from a marine Fusarium species

Area of Science:

• Marine Natural Products Chemistry
• Fungal Metabolomics
• Peptide Structure Elucidation

Background:

• Marine-derived fungi are a rich source of novel bioactive compounds.
• Cyclic tetrapeptides, such as HC-toxin, are known for their biological activities.
• Fusarium species are increasingly recognized for producing diverse secondary metabolites.

Purpose of the Study:

• To isolate and characterize new natural products from marine-derived fungi.
• To elucidate the structure and stereochemistry of a novel cyclic tetrapeptide, JM47.
• To investigate the relationship of JM47 to known peptide families like HC-toxin.

Main Methods:

• Extraction and isolation of metabolites from brown rice cultures of a marine Fusarium species.
• Structure determination of JM47 using advanced NMR techniques (15N HMQC, 15N HMBC, NOESY).
• Stereochemical analysis employing Mosher ester methodology, molecular modeling, and chiral TLC.

Main Results:

• Isolation and identification of enniatin B and a new cyclic tetrapeptide, JM47.
• JM47 was structurally characterized as cyclo(Ala-Ala-Aoh-Pro), with Aoh being (2S,9S)-2-amino-8-oxo-9-hydroxydecanoic acid.
• The study determined the absolute stereochemistry of the Aoh side chain and the tetrapeptide core, revealing an L-, D-, L-, D-configuration.

Conclusions:

• JM47 represents a novel analogue of HC-toxin, featuring an Aoh residue instead of the typical epoxydecanoic acid unit.
• This discovery highlights a marine Fusarium species as a source of complex cyclic tetrapeptides.
• The findings expand the known structural diversity within the HC-toxin family of natural products.