Developing a genetic system for functional manipulations of FUM1, a polyketide synthase gene for the biosynthesis of fumonisins in Fusarium verticillioides

Fengan Yu, Xiangcheng Zhu, Liangcheng Du

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Fumonisins are mycotoxins produced by Fusarium verticillioides, a filamentous fungus that is a widespread pathogen of corn. The biosynthesis of fumonisins is catalyzed by an iterative modular polyketide synthase (PKS). The study of the biosynthetic mechanism for these reduced fungal polyketides has been challenging due to the difficulties in detecting the intermediates with a linear carbon chain and manipulating the 7-domain PKS gene from the filamentous fungus. Here, we described the development of a genetic system for functionally manipulating the methyltransferase domain of FUM1 that is responsible for the assembly of a dimethylated 18-carbon chain. Using a two-stage screening strategy, including both positive and negative screenings, we were able to generate mutant strains with a specifically changed active-site in FUM1. LC-MS analyses indicated that biosynthetic intermediates were detectable in the early stage of culture. The results represent the first functional manipulation of the PKS involved in the biosynthesis of fumonisins.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalFEMS Microbiology Letters
Volume248
Issue number2
DOIs
StatePublished - Jul 15 2005

Fingerprint

Polyketide Synthases
Fumonisins
Fusarium
Fungi
Carbon
Genes
Polyketides
Mycotoxins
Methyltransferases
Zea mays
Catalytic Domain

Keywords

  • Fumonisin
  • Fusarium verticillioides
  • Mycotoxin
  • Polyketide synthase

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology
  • Genetics

Cite this

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abstract = "Fumonisins are mycotoxins produced by Fusarium verticillioides, a filamentous fungus that is a widespread pathogen of corn. The biosynthesis of fumonisins is catalyzed by an iterative modular polyketide synthase (PKS). The study of the biosynthetic mechanism for these reduced fungal polyketides has been challenging due to the difficulties in detecting the intermediates with a linear carbon chain and manipulating the 7-domain PKS gene from the filamentous fungus. Here, we described the development of a genetic system for functionally manipulating the methyltransferase domain of FUM1 that is responsible for the assembly of a dimethylated 18-carbon chain. Using a two-stage screening strategy, including both positive and negative screenings, we were able to generate mutant strains with a specifically changed active-site in FUM1. LC-MS analyses indicated that biosynthetic intermediates were detectable in the early stage of culture. The results represent the first functional manipulation of the PKS involved in the biosynthesis of fumonisins.",
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AU - Zhu, Xiangcheng

AU - Du, Liangcheng

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N2 - Fumonisins are mycotoxins produced by Fusarium verticillioides, a filamentous fungus that is a widespread pathogen of corn. The biosynthesis of fumonisins is catalyzed by an iterative modular polyketide synthase (PKS). The study of the biosynthetic mechanism for these reduced fungal polyketides has been challenging due to the difficulties in detecting the intermediates with a linear carbon chain and manipulating the 7-domain PKS gene from the filamentous fungus. Here, we described the development of a genetic system for functionally manipulating the methyltransferase domain of FUM1 that is responsible for the assembly of a dimethylated 18-carbon chain. Using a two-stage screening strategy, including both positive and negative screenings, we were able to generate mutant strains with a specifically changed active-site in FUM1. LC-MS analyses indicated that biosynthetic intermediates were detectable in the early stage of culture. The results represent the first functional manipulation of the PKS involved in the biosynthesis of fumonisins.

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KW - Fusarium verticillioides

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KW - Polyketide synthase

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