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)

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)6860-6867
Number of pages8
JournalBiochemistry
Volume57
Issue number50
Early online date19 Nov 2018
DOIs
Publication statusPublished - 2018

Fingerprint

Dimethylallyltranstransferase
Prenylation
Biosynthetic Pathways
Tryptophan
Enzymes
Multigene Family
Biological Products
Genes
Anabaena
Biosynthesis
Peptides
Substrates

Keywords

  • Anacyclamides
  • Anabaena
  • tryptophan prenylation
  • cyanobactins
  • ABBA aromatic prenyltransferase
  • N-prenylation

Cite this

Dalponte, L., Parajuli, A., Younger, E., Mattila, A., Jokela, J., Wahlsten, M., ... Fewer, D. P. (2018). N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway. Biochemistry, 57(50), 6860-6867. https://doi.org/10.1021/acs.biochem.8b00879

N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway. / Dalponte, Luca; Parajuli, Anirudra; Younger, Ellen; Mattila, Antti; Jokela, Jouni; Wahlsten, Matti; Leikoski, Niina; Sivonen, Kaarina; Jarmusch, Scott A.; Houssen, Wael E. (Corresponding Author); Fewer, David P. (Corresponding Author).

In: Biochemistry, Vol. 57, No. 50, 2018, p. 6860-6867.

Research output: Contribution to journalArticle

Dalponte, L, Parajuli, A, Younger, E, Mattila, A, Jokela, J, Wahlsten, M, Leikoski, N, Sivonen, K, Jarmusch, SA, Houssen, WE & Fewer, DP 2018, 'N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway', Biochemistry, vol. 57, no. 50, pp. 6860-6867. https://doi.org/10.1021/acs.biochem.8b00879
Dalponte, Luca ; Parajuli, Anirudra ; Younger, Ellen ; Mattila, Antti ; Jokela, Jouni ; Wahlsten, Matti ; Leikoski, Niina ; Sivonen, Kaarina ; Jarmusch, Scott A. ; Houssen, Wael E. ; Fewer, David P. / N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway. In: Biochemistry. 2018 ; Vol. 57, No. 50. pp. 6860-6867.
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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.",
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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.",
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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

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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

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DO - 10.1021/acs.biochem.8b00879

M3 - Article

VL - 57

SP - 6860

EP - 6867

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 50

ER -