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Functional replacement of the ketosynthase domain of FUM1 for the biosynthesis of fumonisins, a group of fungal reduced polyketides

  • Original Paper
  • Published:
Journal of Industrial Microbiology and Biotechnology

Abstract

The genetic manipulation of the biosynthesis of fungal reduced polyketides has been challenging due to the lack of knowledge on the biosynthetic mechanism, the difficulties in the detection of the acyclic, non-aromatic metabolites, and the complexity in genetically manipulating filamentous fungi. Fumonisins are a group of economically important mycotoxins that contaminate maize-based food and feed products worldwide. Fumonisins contain a linear dimethylated C18 chain that is synthesized by Fum1p, which is a single module polyketide synthase (PKS). Using a genetic system that allows the specific manipulation of PKS domains in filamentous fungus Fusarium verticillioides, we replaced the KS domain of fumonisin FUM1 with the KS domain of T-toxin PKS1 from Cochliobolus heterostrophus. Although PKS1 synthesizes different polyketides, the F. verticillioides strain carrying the chimeric PKS produced fumonisins. This represents the first successful domain swapping in PKSs for fungal reduced polyketides and suggests that KS domain alone may not be sufficient to control the product’s structure. To further test if the whole fumonisin PKS could be functionally replaced by a PKS that has a similar domain architecture, we replaced entire FUM1 with PKS1. This strain did not produce any fumonisin or new metabolites, suggesting that the intrinsic interactions between the intact PKS and downstream enzymes in the biosynthetic pathway may play a role in the control of fungal reduced polyketides.

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Acknowledgments

We thank Drs. R. H. Proctor and R. D. Plattner at USDA, Peoria, IL, for providing Cos6B and standard fumonisins, Drs. O. C. Yoder and B. G. Turgeon at Cornell University, Ithaca, NY, for pF5P1, and Dr. David G. Gilchrist at University of California, Davis, CA, USA, for F. verticillioides wild-type strain A0149. Drs. Ron Cerny and Kurt Wulser at Nebraska Center for Mass Spectrometry, University of Nebraska-Lincoln, provided technical assistance in LC-ESMS analyses. This work was supported in part by an Oversea Young Scholar Cooperation Research Fund from the National Natural Science Foundation of China (No. 30428023), a Nebraska Redox Biology Center Pilot grant, and a NSF EPSCOR II grant.

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  1. Chemistry Department, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA

    X. Zhu, F. Yu, R. S. Bojja, K. Zaleta-Rivera & L. Du

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  1. X. Zhu
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  2. F. Yu
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  3. R. S. Bojja
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  4. K. Zaleta-Rivera
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  5. L. Du
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Correspondence to L. Du.

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Zhu, X., Yu, F., Bojja, R.S. et al. Functional replacement of the ketosynthase domain of FUM1 for the biosynthesis of fumonisins, a group of fungal reduced polyketides. J IND MICROBIOL BIOTECHNOL 33, 859–868 (2006). https://doi.org/10.1007/s10295-006-0137-9

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  • DOI: https://doi.org/10.1007/s10295-006-0137-9

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