Discovery and genetic identification of amphiphilic coprogen siderophores from Trichoderm hypoxylon.

Siderophores are small molecular iron chelators and participate in the multiple cellular processes in fungi. In this study, we discovered and identified five amphiphilic coprogen siderophores including three new natural products according to LC-MS-guided separation strategy from Trichoderm hypoxylon. The structures of three new coprogens were elucidated by NMR spectroscopy, and high-resolution (HR)-ESI-MS analysis. Genetic deletions of dfcA and dfcB abolished the production of compounds 1-5 that implied their involvement in the biosynthesis of coprogens. Interestingly, cultivations of ΔdfcA and ΔdfcB mutants with pathogenic fungi Fusarium oxysporum and Mucor corcinelloides showed the weaker inhibitions in comparison to wild type that demonstrated coprogen's role in combating the pathogenic fungi. Our study not only enriched the diversities of siderophores but also provided an approach for finding the rare amphiphilic coprogen siderophores in fungi. Furthermore, this work provided a basis for investigation on the biosynthesis of fungal amphiphilic siderophores and their ecological roles in nature. KEY POINTS: • A series of amphiphilic coprogens were found. • The gene cluster of amphiphilic coprogens and ecological roles were elucidated.