Detoxification of Ustiloxin A Through Oxidative Deamination and Decarboxylation by Endophytic Fungus Petriella setifera

Ustiloxins are a group of cyclopeptide mycotoxins produced by rice false smut pathogen <i>Villosiclava virens</i> (anamorph: <i>Ustilaginoidea virens</i>) which seriously threaten the safety production of rice and the health of humans and livestock. Ustiloxin A, accounting for 60% of the total ustiloxins, is the main toxic component. Biotransformation, a process of modifying the functional groups of compounds by means of regio- or stereo-specific reactions catalyzed by the enzymes produced by organisms, has been considered as an efficient way to detoxify mycotoxins. In this study, the endophytic fungus <i>Petriella setifera</i> Nitaf10 was found to be able to detoxify ustiloxin A through biotransformation. Two transformed products were obtained by using the cell-free extract (CFE) containing intracellular enzymes of <i>P. setifera</i> Nitaf10. They were structurally characterized as novel ustiloxin analogs named ustiloxins A1 (<b>1</b>) and A2 (<b>2</b>) by analysis of the 1D and 2D NMR and HRESIMS spectra as well as by comparison with known ustiloxins. The cytotoxic activity of ustiloxins A1 (<b>1</b>) and A2 (<b>2</b>) was much weaker than that of ustiloxin A. The biotransformation of ustiloxin A was found to proceed via oxidative deamination and decarboxylation and was possibly catalyzed by the intracellular amine oxidase and oxidative decarboxylase in the CFE. An appropriate bioconversion was achieved by incubating ustiloxin A with the CFE prepared in 0.5 mol/L phosphate buffer (pH 7.0) for 24 to 48 h. The optimum initial pH values for the bioconversion of ustiloxin A were 7-9. Among eight metal ions (Co²⁺, Cu²⁺, Fe³⁺, Zn²⁺, Ba²⁺, Ca²⁺, Mg²⁺ and Mn²⁺) tested at 5 mmol/L, Cu²⁺, Fe³⁺ and Zn²⁺ totally inhibited the conversion of ustiloxin A. In conclusion, detoxification of ustiloxin A through oxidative deamination and decarboxylation is an efficient strategy.