A New Siderophore Isolated from Streptomyces sp TM-34 with Potent Inhibitory Activity Against Angiotensin-Converting Enzyme

A new siderophore named tsukubachelin was isolated from an iron-deficient culture medium of newly isolated strain Streptomyces sp. TM-34. The chemical structure of tsukubachelin was established by the interpretation of 2D NMR and TOF-Mass spectroscopic data. The structure of tsukubachelin consists of six amino acid residues, including three serine, and one each of N-alpha-methyl-N-delta-hydroxy-N-delta-formylornithine, N-alpha-methyl-N-delta-hydroxyornithine, and cyclic N-hydroxyornithine. Because the structurally related siderophore, desferri-foroximithine, was reported to have potent angiotensin-converting enzyme inhibition activity, the inhibitory activity of desferri-tsukubachelin and desferri-foroximithine were tested for structure-activity comparison. Desferri-tsukubachelin showed 14 times more potent inhibitory activity than desferri-foroximithine. This result indicates that desferri-tsukubachelin may become a promising agent for angiotensin-converting enzyme inhibition.