Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

A bidomain nonribosomal peptide synthetase encoded by FUM14 catalyzes the formation of tricarballylic esters in the biosynthesis of fumonisins.

Zaleta-Rivera K., Xu C., Yu F., Butchko R.A., Proctor R.H., Hidalgo-Lara M.E., Raza A., Dussault P.H., Du L.

Fumonisins are a group of polyketide-derived mycotoxins produced by Fusarium verticillioides, a filamentous fungus infecting corn and contaminating food and feeds. Fumonisins contain two tricarballylic esters that are critical for toxicity. Here, we present genetic and biochemical data for the esterification mechanism. FUM14 in F. verticillioides has been deleted by homologous recombination, and the resultant mutant lost the ability to produce fumonisins. Two new metabolites, HFB(3) and HFB(4), which are biosynthetic precursors of fumonisins lacking the tricarballylic esters, were detected in the mutant. The results suggest that FUM14 is required for the esterification of fumonisins. FUM14 was predicted to encode a nonribosomal peptide synthetase (NRPS) containing two domains, peptidyl carrier protein and condensation domain. Both the intact Fum14p and the condensation domain have been expressed in Escherichia coli and purified for activity assays. Fum14p was able to convert HFB(3) and HFB(4) to the tricarballylic esters-containing fumonisins, FB(3) and FB(4), respectively, when incubated with tricarballylic thioester of N-acetylcysteamine. In addition, the condensation domain was able to convert HFB(1) to FB(1). These data provide direct evidence for the role of Fum14p in the esterification of fumonisins. More interestingly, the results are the first example of an NRPS condensation domain catalyzing a C-O bond (ester) formation, instead of the typical C-N bond (amide) formation in nonribosomal peptides. The understanding of the esterification mechanism provides useful knowledge for mycotoxin reduction and elimination. The study also provides new insight into the reactions catalyzed by NRPS.

Biochemistry 45:2561-2569(2006) [PubMed] [Europe PMC]

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again