Document Detail

Functional replacement of the ketosynthase domain of FUM1 for the biosynthesis of fumonisins, a group of fungal reduced polyketides.
MedLine Citation:
PMID:  16683125     Owner:  NLM     Status:  MEDLINE    
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.
X Zhu; F Yu; R S Bojja; K Zaleta-Rivera; L Du
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-05-09
Journal Detail:
Title:  Journal of industrial microbiology & biotechnology     Volume:  33     ISSN:  1367-5435     ISO Abbreviation:  J. Ind. Microbiol. Biotechnol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-08-31     Completed Date:  2006-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9705544     Medline TA:  J Ind Microbiol Biotechnol     Country:  England    
Other Details:
Languages:  eng     Pagination:  859-68     Citation Subset:  IM    
Chemistry Department, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA.
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MeSH Terms
Amino Acid Sequence
Ascomycota / enzymology,  genetics*
Fumonisins / metabolism*
Fusarium / enzymology*
Molecular Sequence Data
Mycotoxins / metabolism
Polyketide Synthases / genetics*,  metabolism
Protein Engineering / methods*
Protein Structure, Tertiary / genetics
Reg. No./Substance:
0/Fumonisins; 0/Mycotoxins; 79956-01-7/Polyketide Synthases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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