Discovery of a single monooxygenase catalyzing the carbamate formation and ring contraction in the biosynthesis of legonmycins

Sheng Huang, Jioji Tabudravu, Somayah Sameer Elsayed, Jeanne Travert, Doe Peace, Ming Him Tong, Kwaku Kyeremeh, Sharon Kelly, Laurent Alain Claude Trembleau, Rainer Peter Ebel, Marcel Jaspars, Yi Yu (Corresponding Author), Hai Deng (Corresponding Author)

Research output: Contribution to journalArticle

14 Citations (Scopus)
6 Downloads (Pure)

Abstract

Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. Herein we report the discovery and characterization of the multifunctional FAD-dependent enzyme LgnC that was biochemically characterized in vitro to convert indolizidine intermediate into pyrrolizidine through an unusual ring expansion/contraction strategy tailoring the biosynthesis of new bacterial PAs, the legonmycins. We also confirmed that the legonmycins originate from non-ribosomal peptide synthetases (NRPS) via genomic-driven analysis, heterologous expression and gene inactivation. This is the first report to disclose the biosynthetic origin of bacterial PAs.
Original languageEnglish
Pages (from-to)12697-12701
Number of pages4
JournalAngewandte Chemie International Edition
Volume54
Issue number43
Early online date17 Jul 2015
DOIs
Publication statusPublished - 19 Oct 2015

Fingerprint

Pyrrolizidine Alkaloids
Alkaloids
Carbamates
Biosynthesis
Mixed Function Oxygenases
Indolizidines
Peptide Synthases
Flavin-Adenine Dinucleotide
Bioactivity
Biological Products
Peptides
Enzymes
Genes

Keywords

  • biosynthesis
  • legonmycins
  • multifunctional enzymes
  • non-ribosomal peptide synthetases
  • pyrrolizidine alkaloids

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Discovery of a single monooxygenase catalyzing the carbamate formation and ring contraction in the biosynthesis of legonmycins. / Huang, Sheng; Tabudravu, Jioji; Elsayed, Somayah Sameer; Travert, Jeanne; Peace, Doe; Tong, Ming Him; Kyeremeh, Kwaku; Kelly, Sharon; Trembleau, Laurent Alain Claude; Ebel, Rainer Peter; Jaspars, Marcel; Yu, Yi (Corresponding Author); Deng, Hai (Corresponding Author).

In: Angewandte Chemie International Edition, Vol. 54, No. 43, 19.10.2015, p. 12697-12701.

Research output: Contribution to journalArticle

Huang, Sheng ; Tabudravu, Jioji ; Elsayed, Somayah Sameer ; Travert, Jeanne ; Peace, Doe ; Tong, Ming Him ; Kyeremeh, Kwaku ; Kelly, Sharon ; Trembleau, Laurent Alain Claude ; Ebel, Rainer Peter ; Jaspars, Marcel ; Yu, Yi ; Deng, Hai. / Discovery of a single monooxygenase catalyzing the carbamate formation and ring contraction in the biosynthesis of legonmycins. In: Angewandte Chemie International Edition. 2015 ; Vol. 54, No. 43. pp. 12697-12701.
@article{5dd4f0310cde4fb2b2fca68e4fe37b63,
title = "Discovery of a single monooxygenase catalyzing the carbamate formation and ring contraction in the biosynthesis of legonmycins",
abstract = "Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. Herein we report the discovery and characterization of the multifunctional FAD-dependent enzyme LgnC that was biochemically characterized in vitro to convert indolizidine intermediate into pyrrolizidine through an unusual ring expansion/contraction strategy tailoring the biosynthesis of new bacterial PAs, the legonmycins. We also confirmed that the legonmycins originate from non-ribosomal peptide synthetases (NRPS) via genomic-driven analysis, heterologous expression and gene inactivation. This is the first report to disclose the biosynthetic origin of bacterial PAs.",
keywords = "biosynthesis, legonmycins, multifunctional enzymes, non-ribosomal peptide synthetases, pyrrolizidine alkaloids",
author = "Sheng Huang and Jioji Tabudravu and Elsayed, {Somayah Sameer} and Jeanne Travert and Doe Peace and Tong, {Ming Him} and Kwaku Kyeremeh and Sharon Kelly and Trembleau, {Laurent Alain Claude} and Ebel, {Rainer Peter} and Marcel Jaspars and Yi Yu and Hai Deng",
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.",
year = "2015",
month = "10",
day = "19",
doi = "10.1002/anie.201502902",
language = "English",
volume = "54",
pages = "12697--12701",
journal = "Angewandte Chemie International Edition",
issn = "1433-7851",
publisher = "WILEY-V C H VERLAG GMBH",
number = "43",

}

TY - JOUR

T1 - Discovery of a single monooxygenase catalyzing the carbamate formation and ring contraction in the biosynthesis of legonmycins

AU - Huang, Sheng

AU - Tabudravu, Jioji

AU - Elsayed, Somayah Sameer

AU - Travert, Jeanne

AU - Peace, Doe

AU - Tong, Ming Him

AU - Kyeremeh, Kwaku

AU - Kelly, Sharon

AU - Trembleau, Laurent Alain Claude

AU - Ebel, Rainer Peter

AU - Jaspars, Marcel

AU - Yu, Yi

AU - Deng, Hai

N1 - 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.

PY - 2015/10/19

Y1 - 2015/10/19

N2 - Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. Herein we report the discovery and characterization of the multifunctional FAD-dependent enzyme LgnC that was biochemically characterized in vitro to convert indolizidine intermediate into pyrrolizidine through an unusual ring expansion/contraction strategy tailoring the biosynthesis of new bacterial PAs, the legonmycins. We also confirmed that the legonmycins originate from non-ribosomal peptide synthetases (NRPS) via genomic-driven analysis, heterologous expression and gene inactivation. This is the first report to disclose the biosynthetic origin of bacterial PAs.

AB - Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. Herein we report the discovery and characterization of the multifunctional FAD-dependent enzyme LgnC that was biochemically characterized in vitro to convert indolizidine intermediate into pyrrolizidine through an unusual ring expansion/contraction strategy tailoring the biosynthesis of new bacterial PAs, the legonmycins. We also confirmed that the legonmycins originate from non-ribosomal peptide synthetases (NRPS) via genomic-driven analysis, heterologous expression and gene inactivation. This is the first report to disclose the biosynthetic origin of bacterial PAs.

KW - biosynthesis

KW - legonmycins

KW - multifunctional enzymes

KW - non-ribosomal peptide synthetases

KW - pyrrolizidine alkaloids

U2 - 10.1002/anie.201502902

DO - 10.1002/anie.201502902

M3 - Article

VL - 54

SP - 12697

EP - 12701

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

SN - 1433-7851

IS - 43

ER -