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Nitrogen deprivation in Fusarium oxysporum promotes mycotoxin production via intermediates in the Krebs cycle and unreported methylmalonyl-CoA mutase activity

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Abstract

Introduction

Fusarium oxysporum has a high affinity for lignin and cellulose-based substrates and is known to grow in a wide range of environments. It is these properties and its ability to produce mycotoxins that have contributed to its pathogenicity in cereal crops that can affect human and animal health when ingested.

Objectives

Identify the mechanisms of mycotoxin production and map the functional output of F. oxysporum under varying growth conditions.

Methods

Liquid and gas-based chromatography coupled with mass spectrometry was used to identify and map the untargeted metabolic pathway of F. oxysporum grown using nitrogen limited and organic/inorganic nitrogen supplemented media.

Results

Over 1300 metabolites were identified, relating to 42 metabolic pathways. Of these, 520 metabolites merged at pyruvate (glycolysis), succinate (Krebs cycle) and aspartate-glutamate metabolic pathways. CoA depletion at the growth stage triggered the initiation of fatty acid and branched amino acid degradation. This in turn activated propionyl CoA carnitine acetyltransferase enzymes, resulting in nitrogen preservation (urea, putrescine and organic acids end-products). CoA then transferred into the TCA cycle via previously unreported β-alanine and propionyl CoA metabolic pathways, the latter likely being a novel methylmalonyl-CoA mutase activity for F. oxysporum.

Conclusions

The lower supplementation of inorganic nitrogen compounds (≤ 50 mM) and the elimination of nitrates/organic nitrogen sources resulted in TCA autophagy events that boosted mycotoxin-based metabolism and decreased overall F. oxysporum growth. Such knowledge of functional mycotoxin production can be used to supplement agricultural crops and reduce the risk of mycotoxin contamination in human and animal food supplies.

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Authors and Affiliations

  1. Land & Water, CSIRO, Ecosciences Precinct, Dutton Park, QLD, 4102, Australia

    A. V. Karpe & D. J. Beale

  2. Technical Development, Seqirus, 63 Poplar Road, Parkville, VIC, 3052, Australia

    M. S. Dunn, T. Nguyen, C. Ong, T. Karla & S. Rockman

  3. Land & Water, CSIRO, Acton, ACT, 2601, Australia

    M. C. Taylor

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  1. A. V. Karpe
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Contributions

AVK and MSD performed the data analysis and co-wrote the paper; MCT performed the LC and GC analysis; TN, CO, and TK isolated the fungi and carried out the fungal experiments; SR and DJB devised and supervised the project. All authors read and approved the manuscript.

Corresponding author

Correspondence to D. J. Beale.

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This article does not contain any studies with human and/or animal participants performed by any of the authors.

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Karpe, A.V., Dunn, M.S., Taylor, M.C. et al. Nitrogen deprivation in Fusarium oxysporum promotes mycotoxin production via intermediates in the Krebs cycle and unreported methylmalonyl-CoA mutase activity. Metabolomics 14, 160 (2018). https://doi.org/10.1007/s11306-018-1459-0

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