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

Yuquan Xu; Rousel Orozco; E. M.Kithsiri Wijeratne; A. A.Leslie Gunatilaka; S. Patricia Stock; István Molnár

doi:10.1016/j.chembiol.2008.07.011

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

Yuquan Xu
, Rousel Orozco
, E. M.Kithsiri Wijeratne
, A. A.Leslie Gunatilaka
, S. Patricia Stock
, István Molnár^*

^*Corresponding author for this work

Not published at VTT

University of Arizona

Research output: Contribution to journal › Article › Scientific › peer-review

218 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 language	English
Pages (from-to)	898-907
Journal	Chemistry and Biology
Volume	15
Issue number	9
DOIs	https://doi.org/10.1016/j.chembiol.2008.07.011
Publication status	Published - 22 Sept 2008
MoE publication type	A1 Journal article-refereed

Funding

Financial support was provided by the Arizona Biomedical Research Commission, and the Center of Insect Science, University of Arizona. R.O. acknowledges support of the Bio5 Institute, University of Arizona. FTICR-MS service was provided by A. Somogyi at the University of Arizona.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CHEMBIO

Access to Document

10.1016/j.chembiol.2008.07.011

Cite this

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

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.",

keywords = "CHEMBIO",

author = "Yuquan Xu and Rousel Orozco and Wijeratne, \{E. M.Kithsiri\} and Gunatilaka, \{A. A.Leslie\} and Stock, \{S. Patricia\} and Istv{\'a}n Moln{\'a}r",

note = "Funding Information: Financial support was provided by the Arizona Biomedical Research Commission, and the Center of Insect Science, University of Arizona. R.O. acknowledges support of the Bio5 Institute, University of Arizona. FTICR-MS service was provided by A. Somogyi at the University of Arizona. ",

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doi = "10.1016/j.chembiol.2008.07.011",

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AU - Xu, Yuquan

AU - Orozco, Rousel

AU - Wijeratne, E. M.Kithsiri

AU - Gunatilaka, A. A.Leslie

AU - Stock, S. Patricia

AU - Molnár, István

N1 - Funding Information: Financial support was provided by the Arizona Biomedical Research Commission, and the Center of Insect Science, University of Arizona. R.O. acknowledges support of the Bio5 Institute, University of Arizona. FTICR-MS service was provided by A. Somogyi at the University of Arizona.

PY - 2008/9/22

Y1 - 2008/9/22

N2 - 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.

AB - 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.

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DO - 10.1016/j.chembiol.2008.07.011

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AN - SCOPUS:51649094295

SN - 1074-5521

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IS - 9

ER -

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

Abstract

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UN SDGs

Keywords

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