Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins

Sheng Huang; Jioji Tabudravu; Somayah S. Elsayed; Jeanne Travert; Doe Peace; Ming Him Tong; Kwaku Kyeremeh; Sharon M. Kelly; Laurent  Trembleau; Rainer  Ebel; Marcel Jaspars; Yi  Yu; Hai Deng

doi:10.1002/anie.201502902

Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins

Sheng Huang, Jioji Tabudravu, Somayah S. Elsayed, Jeanne Travert, Doe Peace, Ming Him Tong, Kwaku Kyeremeh, Sharon M. Kelly, Laurent Trembleau, Rainer Ebel, Marcel Jaspars, Yi Yu^* (Corresponding Author), Hai Deng^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization of the multifunctional FAD‐dependent enzyme LgnC is now described. The enzyme is shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial PAs, the so‐called legonmycins. By genome‐driven analysis, heterologous expression, and gene inactivation, the legonmycins were also shown to originate from non‐ribosomal peptide synthetases (NRPSs). The biosynthetic origin of bacterial PAs has thus been disclosed for the first time.

Original language	English
Pages (from-to)	12697-12701
Number of pages	5
Journal	Angewandte Chemie International Edition
Volume	54
Issue number	43
Early online date	17 Jul 2015
DOIs	https://doi.org/10.1002/anie.201502902
Publication status	Published - 19 Oct 2015

Bibliographical note

Acknowledgements
Y.Y. acknowledges financial support from the “973” Program (2012CB721006) and the National Natural Science Foundation of China (81102357). M.J., R.E., K.K., and H.D. acknowledge the Leverhulme Trust-Royal Society Africa (AA090088). J.T., R.E., M.J., Y.Y., and H.D. are grateful for financial support through the EU Seventh Framework Programme (312184). S.S.E. thanks the Egyptian Government for financial support of the PhD studies. We thank Dr. Richard Hodgson, Phenomenex, UK for HPLC analysis.

Keywords

biosynthesis
legonmycins
multifunctional enzymes
non-ribosomal peptide synthetases
pyrrolizidine alkaloids

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10.1002/anie.201502902Licence: Unspecified

Hai Deng
- School of Natural & Computing Sciences, Chemistry - Personal Chair
Person: Academic
Laurent Trembleau
- School of Natural & Computing Sciences, Chemistry - Senior Lecturer
Person: Academic

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Huang, S., Tabudravu, J., Elsayed, S. S., Travert, J., Peace, D., Tong, M. H., Kyeremeh, K., Kelly, S. M., Trembleau, L., Ebel, R., Jaspars, M., Yu, Y., & Deng, H. (2015). Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins. Angewandte Chemie International Edition, 54(43), 12697-12701. https://doi.org/10.1002/anie.201502902

Huang, S, Tabudravu, J, Elsayed, SS, Travert, J, Peace, D, Tong, MH, Kyeremeh, K, Kelly, SM, Trembleau, L , Ebel, R , Jaspars, M, Yu, Y & Deng, H 2015, 'Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins', Angewandte Chemie International Edition, vol. 54, no. 43, pp. 12697-12701. https://doi.org/10.1002/anie.201502902

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abstract = "Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization of the multifunctional FAD‐dependent enzyme LgnC is now described. The enzyme is shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial PAs, the so‐called legonmycins. By genome‐driven analysis, heterologous expression, and gene inactivation, the legonmycins were also shown to originate from non‐ribosomal peptide synthetases (NRPSs). The biosynthetic origin of bacterial PAs has thus been disclosed for the first time.",

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note = "Acknowledgements Y.Y. acknowledges financial support from the “973” Program (2012CB721006) and the National Natural Science Foundation of China (81102357). M.J., R.E., K.K., and H.D. acknowledge the Leverhulme Trust-Royal Society Africa (AA090088). J.T., R.E., M.J., Y.Y., and H.D. are grateful for financial support through the EU Seventh Framework Programme (312184). S.S.E. thanks the Egyptian Government for financial support of the PhD studies. We thank Dr. Richard Hodgson, Phenomenex, UK for HPLC analysis.",

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N2 - Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization of the multifunctional FAD‐dependent enzyme LgnC is now described. The enzyme is shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial PAs, the so‐called legonmycins. By genome‐driven analysis, heterologous expression, and gene inactivation, the legonmycins were also shown to originate from non‐ribosomal peptide synthetases (NRPSs). The biosynthetic origin of bacterial PAs has thus been disclosed for the first time.

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Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins

Abstract

Bibliographical note

Keywords

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