Biosynthesis of the Cyclooligomer Depsipeptide Beauvericin, a Virulence Factor of the Entomopathogenic Fungus Beauveria bassiana

Yuquan Xu, Rousel Orozco, E. M Kithsiri Wijeratne, Leslie Gunatilaka, S Patricia Stock, Istvan Molnar

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Beauvericin, a cyclohexadepsipeptide ionophore from the entomopathogen Beauveria bassiana, shows antibiotic, antifungal, insecticidal, and cancer cell antiproliferative and antihaptotactic (cell motility inhibitory) activity in vitro. The bbBeas gene encoding the BbBEAS nonribosomal peptide synthetase was isolated from B. bassiana and confirmed to be responsible for beauvericin biosynthesis by targeted disruption. BbBEAS utilizes D-2-hydroxyisovalerate (D-Hiv) and L-phenylalanine (Phe) for the iterative synthesis of a predicted N-methyl-dipeptidol intermediate, and forms the cyclic trimeric ester beauvericin from this intermediate in an unusual recursive process. Heterologous expression of the bbBeas gene in Escherichia coli to produce the 3189 amino acid, 351.9 kDa BbBEAS enzyme provided a strain proficient in beauvericin biosynthesis. Comparative infection assays with a BbBEAS knockout B. bassiana strain against three insect hosts revealed that beauvericin plays a highly significant but not indispensable role in virulence.

Original languageEnglish (US)
Pages (from-to)898-907
Number of pages10
JournalChemistry and Biology
Volume15
Issue number9
DOIs
StatePublished - Sep 22 2008

Fingerprint

Beauveria
Depsipeptides
Biosynthesis
Virulence Factors
Fungi
Peptide Synthases
Gene encoding
Antifungal Agents
Ionophores
Phenylalanine
Escherichia coli
Cell Movement
Virulence
Insects
Assays
Esters
Genes
Cells
beauvericin
Gene Expression

Keywords

  • CHEMBIO

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Biosynthesis of the Cyclooligomer Depsipeptide Beauvericin, a Virulence Factor of the Entomopathogenic Fungus Beauveria bassiana. / Xu, Yuquan; Orozco, Rousel; Wijeratne, E. M Kithsiri; Gunatilaka, Leslie; Stock, S Patricia; Molnar, Istvan.

In: Chemistry and Biology, Vol. 15, No. 9, 22.09.2008, p. 898-907.

Research output: Contribution to journalArticle

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