New ferrichrome-type siderophores produced by Fusarium lateritium cultured on sodium nitrate-supplemented rice medium

Iron is an essential element for all living organisms, and various microorganisms, such as fungi and bacteria, produce siderophores that chelate iron and facilitate its uptake from the environment. Certain fungi produce ferrichrome-type cyclic hexapeptides containing three N^δ-acetyl-N^δ-hydroxyornithine residues as siderophores. In this study, we found that adding sodium nitrate to solid rice culture medium induced the production of several new ferrichrome-type siderophores in Fusarium lateritium (18F04506), isolated from tidal flat soil in Kumamoto, Japan. LC-MS-guided fractionation of the culture extract afforded two new metabolites, named fusariferins A and B. Their planar structures were determined by detailed analysis of 1D and 2D NMR spectra, and the absolute configurations of the amino acids were determined using Marfey's method. Furthermore, we demonstrated that these compounds were produced by the fungus only when cultured on rice medium supplemented with sodium nitrate, but not on medium supplemented with ammonium chloride, ammonium sulfate, or ammonium nitrate. These findings not only expand the structural diversity of fungal siderophores through the discovery of new ferrichrome-type compounds but also provide new insights into the nitrogen-dependent regulatory mechanism of siderophore biosynthesis in fungi.