N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway

Luca Dalponte; Anirudra Parajuli; Ellen Younger; Antti Mattila; Jouni Jokela; Matti Wahlsten; Niina Leikoski; Kaarina Sivonen; Scott A. Jarmusch; Wael E. Houssen; David P. Fewer

doi:10.1021/acs.biochem.8b00879

N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway

Luca Dalponte, Anirudra Parajuli, Ellen Younger, Antti Mattila, Jouni Jokela, Matti Wahlsten, Niina Leikoski, Kaarina Sivonen, Scott A. Jarmusch, Wael E. Houssen (Corresponding Author), David P. Fewer (Corresponding Author)

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Abstract

Aromatic prenylation is an important step in the biosynthesis of many natural products and leads to an astonishing diversity of chemical structures. Cyanobactin pathways frequently encode aromatic prenyltransferases that catalyze the prenylation of these macrocyclic and linear peptides. Here we characterized the anacyclamide (acy) biosynthetic gene cluster from Anabaena sp. UHCC-0232. Partial reconstitution of the anacyclamide pathway, heterologous expression and in vitro biochemical characterization of the enzyme demonstrate that the AcyF enzyme encoded in this biosynthetic gene cluster is a Trp N-prenyltransferase. Phylogenetic analysis suggests the monophyletic origin and rapid diversification of the cyanobactin prenyltransferase enzymes and the multiple origins of N-1 Trp prenylation in prenylated natural products. The AcyF enzyme displayed high flexibility towards a range of Trp-containing substrates and represents an interesting new tool for biocatalytic applications.

Original language	English
Pages (from-to)	6860-6867
Number of pages	8
Journal	Biochemistry
Volume	57
Issue number	50
Early online date	19 Nov 2018
DOIs	https://doi.org/10.1021/acs.biochem.8b00879
Publication status	Published - 2018

Keywords

Anacyclamides
Anabaena
tryptophan prenylation
cyanobactins
ABBA aromatic prenyltransferase
N-prenylation

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.biochem.8b00879.
Accepted author manuscript, 2.2 MBLicence: Unspecified

Wael E Houssen
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Reader
- Institute of Medical Sciences
Person: Academic

Aberdeen Proteomics
David Stead (Manager)
Medical Sciences
Research Facilities: Facility
Marine Biodiscovery Centre
Marcel Jaspars (Manager)
The Marine Biodiscovery Centre
Research Facilities: Facility

Cite this

@article{fb0070e26c8940979b2b8a62f54e0c12,

title = "N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway",

abstract = "Aromatic prenylation is an important step in the biosynthesis of many natural products and leads to an astonishing diversity of chemical structures. Cyanobactin pathways frequently encode aromatic prenyltransferases that catalyze the prenylation of these macrocyclic and linear peptides. Here we characterized the anacyclamide (acy) biosynthetic gene cluster from Anabaena sp. UHCC-0232. Partial reconstitution of the anacyclamide pathway, heterologous expression and in vitro biochemical characterization of the enzyme demonstrate that the AcyF enzyme encoded in this biosynthetic gene cluster is a Trp N-prenyltransferase. Phylogenetic analysis suggests the monophyletic origin and rapid diversification of the cyanobactin prenyltransferase enzymes and the multiple origins of N-1 Trp prenylation in prenylated natural products. The AcyF enzyme displayed high flexibility towards a range of Trp-containing substrates and represents an interesting new tool for biocatalytic applications.",

keywords = "Anacyclamides, Anabaena, tryptophan prenylation, cyanobactins, ABBA aromatic prenyltransferase, N-prenylation",

author = "Luca Dalponte and Anirudra Parajuli and Ellen Younger and Antti Mattila and Jouni Jokela and Matti Wahlsten and Niina Leikoski and Kaarina Sivonen and Jarmusch, {Scott A.} and Houssen, {Wael E.} and Fewer, {David P.}",

note = "Funding This work was supported by grants from the Academy of Finland (259505, D.P.F.), Helsinki University Research grant (490085, D.P.F.) ESCMID grant (4720572, D.P.F.), the Industrial Biotechnology Innovation Centre (IBioIC) studentship (L. D.), the Jane and Aatos Erkko Foundation (K.S.), the BBSRC FoF grant (no BB/M013669/1, W. E. H.), IBCatalyst grant (no. BB/M028526/1, W. E. H.), the Sarcoma UK grant (W. E. H.) and the SULSA Leaders and SULSA PECRE awards (W. E. H.). W. E. H. acknowledges the fund from the ERC grant no. 339367. ACKNOWLEDGEMENTS D.P.F. and K.S. are grateful to Lyudmila Saari, Department of Microbiology, University of Helsinki, for her valuable help in handling the Anabaena sp. UHCC-0232 culture. W. E. H. thanks the Aberdeen Proteomics Facility and the Marine Biodiscovery Centre Mass Spectrometry Facility for extensive MS analysis. W. E. H. is grateful to Mr. Russell Gray (Marine Biodiscovery Centre, University of Aberdeen) for the NMR analysis of our samples.",

year = "2018",

doi = "10.1021/acs.biochem.8b00879",

language = "English",

volume = "57",

pages = "6860--6867",

journal = "Biochemistry",

issn = "0006-2960",

publisher = "American Chemical Society",

number = "50",

}

TY - JOUR

T1 - N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway

AU - Dalponte, Luca

AU - Parajuli, Anirudra

AU - Younger, Ellen

AU - Mattila, Antti

AU - Jokela, Jouni

AU - Wahlsten, Matti

AU - Leikoski, Niina

AU - Sivonen, Kaarina

AU - Jarmusch, Scott A.

AU - Houssen, Wael E.

AU - Fewer, David P.

N1 - Funding This work was supported by grants from the Academy of Finland (259505, D.P.F.), Helsinki University Research grant (490085, D.P.F.) ESCMID grant (4720572, D.P.F.), the Industrial Biotechnology Innovation Centre (IBioIC) studentship (L. D.), the Jane and Aatos Erkko Foundation (K.S.), the BBSRC FoF grant (no BB/M013669/1, W. E. H.), IBCatalyst grant (no. BB/M028526/1, W. E. H.), the Sarcoma UK grant (W. E. H.) and the SULSA Leaders and SULSA PECRE awards (W. E. H.). W. E. H. acknowledges the fund from the ERC grant no. 339367. ACKNOWLEDGEMENTS D.P.F. and K.S. are grateful to Lyudmila Saari, Department of Microbiology, University of Helsinki, for her valuable help in handling the Anabaena sp. UHCC-0232 culture. W. E. H. thanks the Aberdeen Proteomics Facility and the Marine Biodiscovery Centre Mass Spectrometry Facility for extensive MS analysis. W. E. H. is grateful to Mr. Russell Gray (Marine Biodiscovery Centre, University of Aberdeen) for the NMR analysis of our samples.

PY - 2018

Y1 - 2018

N2 - Aromatic prenylation is an important step in the biosynthesis of many natural products and leads to an astonishing diversity of chemical structures. Cyanobactin pathways frequently encode aromatic prenyltransferases that catalyze the prenylation of these macrocyclic and linear peptides. Here we characterized the anacyclamide (acy) biosynthetic gene cluster from Anabaena sp. UHCC-0232. Partial reconstitution of the anacyclamide pathway, heterologous expression and in vitro biochemical characterization of the enzyme demonstrate that the AcyF enzyme encoded in this biosynthetic gene cluster is a Trp N-prenyltransferase. Phylogenetic analysis suggests the monophyletic origin and rapid diversification of the cyanobactin prenyltransferase enzymes and the multiple origins of N-1 Trp prenylation in prenylated natural products. The AcyF enzyme displayed high flexibility towards a range of Trp-containing substrates and represents an interesting new tool for biocatalytic applications.

AB - Aromatic prenylation is an important step in the biosynthesis of many natural products and leads to an astonishing diversity of chemical structures. Cyanobactin pathways frequently encode aromatic prenyltransferases that catalyze the prenylation of these macrocyclic and linear peptides. Here we characterized the anacyclamide (acy) biosynthetic gene cluster from Anabaena sp. UHCC-0232. Partial reconstitution of the anacyclamide pathway, heterologous expression and in vitro biochemical characterization of the enzyme demonstrate that the AcyF enzyme encoded in this biosynthetic gene cluster is a Trp N-prenyltransferase. Phylogenetic analysis suggests the monophyletic origin and rapid diversification of the cyanobactin prenyltransferase enzymes and the multiple origins of N-1 Trp prenylation in prenylated natural products. The AcyF enzyme displayed high flexibility towards a range of Trp-containing substrates and represents an interesting new tool for biocatalytic applications.

KW - Anacyclamides

KW - Anabaena

KW - tryptophan prenylation

KW - cyanobactins

KW - ABBA aromatic prenyltransferase

KW - N-prenylation

U2 - 10.1021/acs.biochem.8b00879

DO - 10.1021/acs.biochem.8b00879

M3 - Article

VL - 57

SP - 6860

EP - 6867

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 50

ER -

N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway

Abstract

Keywords

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Wael E Houssen

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Aberdeen Proteomics

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