Structure of trichamide, a cyclic peptide from the bloom-forming cyanobacterium Trichodesmium erythraeum, predicted from the genome sequence

Abstract

A gene cluster for the biosynthesis of a new small cyclic peptide, dubbed trichamide, was discovered in the genome of the global, bloom-forming marine cyanobacterium Trichodesmium erythraeum ISM101 because of striking similarities to the previously characterized patellamide biosynthesis cluster. The tri cluster consists of a precursor peptide gene containing the amino acid sequence for mature trichamide, a putative heterocyclization gene, an oxidase, two proteases, and hypothetical genes. Based upon detailed sequence analysis, a structure was predicted for trichamide and confirmed by Fourier transform mass spectrometry. Trichamide consists of 11 amino acids, including two cysteine-derived thiazole groups, and is cyclized by an N C terminal amide bond. As the first natural product reported from T. erythraeum, trichamide shows the power of genome mining in the prediction and discovery of new natural products.

FIG. 1.

The tri gene cluster. Arrows denote ORFs and their direction. Black ORFs are tRNA synthetases, white ORFs are conserved hypothetical genes without a homolog in the pat cluster, green ORFs are pat homologs, and the gene encoding the precursor peptide is orange.

FIG. 2.

Alignment of the precursor peptides PatE and TriG. The sequences encoding patellamide C, patellamide A, and trichamide (top to bottom) are underlined, and the proposed cyclization signals are in boldface type.

FIG. 3.

(A) Structure of trichamide. Stereochemistry is inferred and not determined experimentally, as described in the text. (B) Assignment of CID-MS fragments from Table 2 to the trichamide structure. (C) Assignment of IRMPD-MS fragments.

FIG. 4.

Proposed biosynthetic pathway to trichamide.