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 NOC 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.

Screening the toxicity and toxin content of blooms of the cyanobacterium Trichodesmium erythraeum (Ehrenberg) in northeast Brasil

“…In the same manner, toxic compounds might limit or restrict the grazing on Trichodesmium by microcrustaceans or even by fish. On the other hand, compounds other than the toxins analyzed, such as MIC and STX analogues, can have similar effects since several components can be produced by the same organisms (6,10,21,24).…”

A global assembly line for cyanobactins

“…By mimicking this natural evolution, a new cyclic peptide was made using rational genetic engineering (1) 6 . A homologous pathway was found in the genome of a free-living cyanobacterium encoding a new natural product, trichamide (2) 7 .…”

“…The patellamides (3)(4)(5)(6)(7)(8) are biosynthesized through a unique ribosomal route 2 with some similarity to microcin pathways ( Fig. 1) 8 .…”

Widespread Occurrence and Lateral Transfer of the Cyanobactin Biosynthesis Gene Cluster in Cyanobacteria

“…Cyanobactins include compounds with antitumor and multidrug reversing activities with potential as drug leads (9,17,19). These bacteriocin-like peptides are produced by cyanobacteria isolated from soil (1,2,17) as well as marine (19,20,22) and freshwater (10,11,25) environments. Cyanobactins are produced through the proteolytic cleavage and macrocyclization of short precursor proteins (7,20,22).…”

“…These bacteriocin-like peptides are produced by cyanobacteria isolated from soil (1,2,17) as well as marine (19,20,22) and freshwater (10,11,25) environments. Cyanobactins are produced through the proteolytic cleavage and macrocyclization of short precursor proteins (7,20,22). The peptide precursor undergoes heterocyclization of threonines, serines, or cysteines during the maturation of the cyclic peptide (7).…”