Mechanistic Insight into the Biosynthesis and Detoxification of Fumonisin Mycotoxins

Abstract

Fumonisins, notably FB1, FB2, FB3, and FB4, are economically important mycotoxins produced by a number Fusarium sp. that occur on corn, rice, and sorghum as well as by Aspergillus sp. on grapes. The fumonisin scaffold is comprised of a C18 polyketide backbone functionalized with two tricarballylic esters and an alanine derived amine. These functional groups contribute to fumonisin's ability to inhibit sphingolipid biosynthesis in animals, plants, and yeasts. We report for the first time the isolation and structure elucidation of two classes of nonaminated fumonisins (FPy and FLa) produced by Aspergillus welwitschiae. Using a Lemna minor (duckweed) bioassay, these new compounds were significantly less toxic in comparison to the fumonisin B mycotoxins, providing new insight into the mechanism of fumonisin toxicity. Time course fermentations monitoring the production of FB4, FPy4, and FLa4, as well as (13)C and (15)N stable isotope incorporation, suggest a novel postbiosynthetic oxidative deamination process for fumonisins. This pathway was further supported by a feeding study with FB1, a fumonisin not produced by Aspergillus sp., which resulted in its transformation to FPy1. This study demonstrates that Aspergillus have the ability to produce enzymes that could be used for fumonisin detoxification.

Detoxification of Mycotoxins through Biotransformation

“…(iii) Oxidative deamination: fumonisn B 4 (FB 4 , 129) was transformed into fumonisins La 4 (Fla 4 , 130) and Py 4 (FPy 4 , 131) through oxidative deamination by Aspergillus sp. Nonaminated Fla 4 (130) and FPy 4 (131) was significantly less toxic in comparison to the fumonisin B mycotoxins, which provided new insight into the mechanism of fumonisin toxicity [106].…”

“…Using a duckweed (Lemna minor) bioassay, both Fla4 (130) and FPy4, (131) were significantly less toxic in comparision to the fumonisin B mycotoxins. This demonstrated that Aspergillus fungi have the ability to produce enzymes that could be used for fumonisin detoxification [106].…”

“…Fumonisin B4 (FB4, 129) was transformed into fumonisins La4 (Fla4, 130) and Py4 (FPy4, 131) through oxidative deamination by Aspergillus sp. ( Figure S66) [106]. Using a duckweed (Lemna minor) bioassay, both Fla4 (130) and FPy4, (131) were significantly less toxic in comparision to the fumonisin B mycotoxins.…”

Strategies and Methodologies for Developing Microbial Detoxification Systems to Mitigate Mycotoxins

“…Beyond showing a reduction in the toxicity of the final biotransformation product(s), the mechanism of this reduction must also be determined [143,144]. For example, the reduction in DON toxicity due to C3 carbon epimerization was attributed to attenuated binding of 3- epi -DON within the ribosomal peptidyl transferase center [139,140], in addition to increased polarity of 3 - epi -DON and decreased molecular interactions with different cellular targets, such as Fusarium graminearum Tri101 acetyltransferase [145].…”

Pre‐ and Postharvest Strategies to Minimize Mycotoxin Contamination in the Rice Food Chain

“…It was found that among five isolates that could degrade CIT without affecting the desirable monacolin K levels, Enterococcus cloacae and Rhizobium borbori were able to decrease CIT from 5 ppm to 1.83 ppm and 2.82 ppm, after 120 hours at 30 °C, respectively (Kanpiengjai, Mahawan, Lumyong, & Khanongnuch, ). Interestingly, also some Aspergillus strains seem to be able to detoxify mycotoxins, in this case through enzyme activity, as it was shown in a study that attested Aspergillus welwitschiae ability to transform fumonisins in nonaminated forms (FPy and FLa), which are much less toxic, addressing possible new approaches in decontamination processes (Burgess, Renaud, McDowell, & Sumarah, ).…”