Metabolic Rewiring Improves the Production of the Fungal Active Targeting Molecule Fusarinine C

Abstract

Author: Recently, increasing research in siderophores has been dedicated to their possible medical applications in diagnostics and therapeutics for human pathogenic infections. Fusarinine C (FsC) is a natural hydroxamate siderophore that harbors three amino groups, which allow the easy chemical modification of FsC for the design of novel multifunctional conjugates. However, low production of FsC has hampered its extensive exploitation.Herein, we rewired the FsC biosynthetic pathway in the Aureobasidium melanogenum HN6.2 strain to achieve a self-supplying l-ornithine with component-simplified and enhanced production of extracellular siderophores, for which the FsC accounted for 94%, its final titer being approximately 1.7 g L–1. The convenient acquisition of FsC effectuated our exploitation for its application. We employed in vitro and in vivo assays to show that FsC is an active targeting molecule that acts on the human pathogenic fungi Trichophyton rubrum and Candida albicans; this demonstrates the potential to use FsC for the development of novel antifungal targeting reagents in the future.