Experimental Evidence for a Metal-Related Function of a Cyanobactin

The cyanobacterium Prochloron didemni produces macrocyclic octapeptides with thiazole and oxazoline heterocycles, known as patellamides. An interesting observation is that Cu²⁺ binding to the patellamides is likely to be related to their biological function. First, we show that Cu^{2 +} injection into Lissoclinum patella increases patG gene expression and patellamide levels in the ascidians. Second, x-ray absorption spectroscopy shows that biological extracts of specimen from the Great Barrier Reef match structurally synthetic carbonato-bridged dicopper(II)-patellamide complexes. Third, patellamides exhibit very high membrane permeability (PAMPA, Caco-2). Combined with intracellular pH data, patellamide-Cu^{2 +} bioactivity in algae, and the absence of many of the typical CO₂ uptake mechanisms in Prochloron, we propose that patellamides facilitate carbonate transport from the ascidians to the cyanobacteria. This provides unprecedented evidence for a link between cyanobactin metal binding and their production and function, suggesting possible novel metal-related roles for marine cyclic peptides.