Chemical and Metagenomic Studies of the Lethal Black Band Disease of Corals Reveal Two Broadly Distributed, Redox-Sensitive Mixed Polyketide/Peptide Macrocycles

Black band disease (BBD), a lethal,
polymicrobial disease consortium
dominated by the cyanobacterium Roseofilum reptotaenium, kills many species of corals worldwide. To uncover chemical signals
or cytotoxins that could be important in proliferation of Roseofilum and the BBD layer, we examined the secondary
metabolites present in geographically diverse collections of BBD from
Caribbean and Pacific coral reefs. Looekeyolide A (1),
a 20-membered macrocyclic compound formed by a 16-carbon polyketide
chain, 2-deamino-2-hydroxymethionine, and d-leucine, and
its autoxidation product looekeyolide B (2) were extracted
as major compounds (∼1 mg g–1 dry wt) from
more than a dozen field-collected BBD samples. Looekeyolides A and
B were also produced by a nonaxenic R. reptotaenium culture under laboratory conditions at similar concentrations. R. reptotaenium genomes that were constructed from four
different metagenomic data sets contained a unique nonribosomal peptide/polyketide
biosynthetic cluster that is likely responsible for the biosynthesis
of the looekeyolides. Looekeyolide A, which readily oxidizes to looekeyolide
B, may play a biological role in reducing H2O2 and other reactive oxygen species that could occur in the BBD layer
as it overgrows and destroys coral tissue.