A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway

doi:10.1002/anie.201509920

. 2016 Mar 7;55(11):3596-9.

doi: 10.1002/anie.201509920. Epub 2016 Feb 5.

A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway

Anirudra Parajuli ¹, Daniel H Kwak ², Luca Dalponte ^{3

4}, Niina Leikoski ¹, Tomas Galica ^{1

5

6}, Ugochukwu Umeobika ³, Laurent Trembleau ³, Andrew Bent ⁷, Kaarina Sivonen ¹, Matti Wahlsten ¹, Hao Wang ¹, Ermanno Rizzi ⁸, Gianluca De Bellis ⁸, James Naismith ⁷, Marcel Jaspars ³, Xinyu Liu ⁹, Wael Houssen ^{10

11

12}, David Peter Fewer ¹³

Affiliations

¹ Microbiology and Biotechnology Division, Department of Food and Environmental Sciences, P.O.Box 56, Viikki Biocenter, Viikinkaari 9, 00014, University of Helsinki, Finland.
² Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
³ Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, AB24 3UE, UK.
⁴ Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
⁵ Institute of Microbiology AS CR, v.v.i., Center ALGATECH, Třeboň, Czech Republic.
⁶ University of South Bohemia, Faculty of Science, Department of Ecosystem Biology, České Budějovice, Czech Republic.
⁷ Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
⁸ Institute for Biomedical Technologies (ITB), National Research Council (CNR), via F.lli Cervi 93, Segrate (MI), Italy.
⁹ Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA. xinyuliu@pitt.edu.
¹⁰ Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, AB24 3UE, UK. w.houssen@abdn.ac.uk.
¹¹ Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK. w.houssen@abdn.ac.uk.
¹² Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. w.houssen@abdn.ac.uk.
¹³ Microbiology and Biotechnology Division, Department of Food and Environmental Sciences, P.O.Box 56, Viikki Biocenter, Viikinkaari 9, 00014, University of Helsinki, Finland. david.fewer@helsinki.fi.

PMID: 26846478
PMCID: PMC5108402
DOI: 10.1002/anie.201509920

A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway

Anirudra Parajuli et al. Angew Chem Int Ed Engl. 2016.

. 2016 Mar 7;55(11):3596-9.

doi: 10.1002/anie.201509920. Epub 2016 Feb 5.

Authors

Anirudra Parajuli ¹, Daniel H Kwak ², Luca Dalponte ^{3

4}, Niina Leikoski ¹, Tomas Galica ^{1

5

6}, Ugochukwu Umeobika ³, Laurent Trembleau ³, Andrew Bent ⁷, Kaarina Sivonen ¹, Matti Wahlsten ¹, Hao Wang ¹, Ermanno Rizzi ⁸, Gianluca De Bellis ⁸, James Naismith ⁷, Marcel Jaspars ³, Xinyu Liu ⁹, Wael Houssen ^{10

11

12}, David Peter Fewer ¹³

Affiliations

¹ Microbiology and Biotechnology Division, Department of Food and Environmental Sciences, P.O.Box 56, Viikki Biocenter, Viikinkaari 9, 00014, University of Helsinki, Finland.
² Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
³ Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, AB24 3UE, UK.
⁴ Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
⁵ Institute of Microbiology AS CR, v.v.i., Center ALGATECH, Třeboň, Czech Republic.
⁶ University of South Bohemia, Faculty of Science, Department of Ecosystem Biology, České Budějovice, Czech Republic.
⁷ Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
⁸ Institute for Biomedical Technologies (ITB), National Research Council (CNR), via F.lli Cervi 93, Segrate (MI), Italy.
⁹ Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA. xinyuliu@pitt.edu.
¹⁰ Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, AB24 3UE, UK. w.houssen@abdn.ac.uk.
¹¹ Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK. w.houssen@abdn.ac.uk.
¹² Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. w.houssen@abdn.ac.uk.
¹³ Microbiology and Biotechnology Division, Department of Food and Environmental Sciences, P.O.Box 56, Viikki Biocenter, Viikinkaari 9, 00014, University of Helsinki, Finland. david.fewer@helsinki.fi.

PMID: 26846478
PMCID: PMC5108402
DOI: 10.1002/anie.201509920

Erratum in

Corrigendum: A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway.
Parajuli A, Kwak DH, Dalponte L, Leikoski N, Galica T, Umeobika U, Trembleau L, Bent A, Sivonen K, Wahlsten M, Wang H, Rizzi E, De Bellis G, Naismith J, Jaspars M, Liu X, Houssen W, Fewer DP. Parajuli A, et al. Angew Chem Int Ed Engl. 2017 Jan 9;56(2):433. doi: 10.1002/anie.201609949. Angew Chem Int Ed Engl. 2017. PMID: 28045232 No abstract available.

Abstract

Cyanobactins are a rapidly growing family of linear and cyclic peptides produced by cyanobacteria. Kawaguchipeptins A and B, two macrocyclic undecapeptides reported earlier from Microcystis aeruginosa NIES-88, are shown to be products of the cyanobactin biosynthetic pathway. The 9 kb kawaguchipeptin (kgp) gene cluster was identified in a 5.26 Mb draft genome of Microcystis aeruginosa NIES-88. We verified that this gene cluster is responsible for the production of the kawaguchipeptins through heterologous expression of the kgp gene cluster in Escherichia coli. The KgpF prenyltransferase was overexpressed and was shown to prenylate C-3 of Trp residues in both linear and cyclic peptides in vitro. Our findings serve to further enhance the structural diversity of cyanobactins to include tryptophan-prenylated cyclic peptides.

Keywords: biosynthesis; cyanobactins; peptides; prenylation; prenyltransferases.

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Figures

Scheme 1

Scheme 1

The cyclic undecapeptides Kawaguchipeptin A (1) and kawaguchipeptin B (2) reported from Microcystis aeruginosa NIES-88. Kawaguchipeptin A contains two C-3 prenylated tryptophans (highlighted).

Figure 1

Figure 1

The kawaguchipeptin biosynthetic pathway in Microcystis aeruginosa NIES-88. (A) The 10 kb biosynthetic gene cluster that consists of six biosynthetic genes (indicated by grey and black) are organized in a single operon and have homology to genes present in other known cyanobactin gene clusters. The open arrows indicate the genes that encode proteins with unknown functions. The kgpE precursor gene (black) encodes the 87 amino-acid precursor protein (B). Three identical copies of the undecapeptide core are encoded by the single precursor gene (highlighted in gray).

Figure 2

Figure 2

Heterologous expression of the kgp operon in E. coli demonstrates that the kgpA-G genes confer the production of 1 and 2 in vivo. Extracted ion chromatographs of LC–HRMS analysis of: Authentic 1 and 2 from M. aeruginosa NIES-88 (1, 2); 2 in E. coli transformed with pDK-kgp1 (3); 1 in E. coli transformed with pDK-kgp1 (4); 1 in E. coli co-transformed with pDK-kgp1 and pMBI and supplied with mevalonolactone 3 (5); and 2 in E. coli co-transformed with pDK-kgp1 and pMBI and supplied with mevalonolactone 3 (6).

See this image and copyright information in PMC

References

1. Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J. Nat Prod Rep. 2013;30:108–160. - PMC - PubMed
1. Sivonen K, Leikoski N, Fewer DP, Jokela J. Appl Microbiol Biotechnol. 2010;86:1213–1225. - PMC - PubMed
1. Leikoski N, Fewer DP, Sivonen K. Appl Environ Microbiol. 2009;75:853–857. - PMC - PubMed
1. Leikoski N, Fewer DP, Jokela J, Wahlsten M, Rouhiainen L, Sivonen K. Appl Environ Microbiol. 2010;76:701–709. - PMC - PubMed
1. Leikoski N, Liu L, Jokela J, Wahlsten M, Gugger M, Calteau A, Permi P, Kerfeld CA, Sivonen K, Fewer DP. Chem Biol. 2013;20:1033–1043. - PubMed

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[1] Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J. Nat Prod Rep. 2013;30:108–160. - PMC - PubMed

[2] Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J. Nat Prod Rep. 2013;30:108–160. - PMC - PubMed

[3] Sivonen K, Leikoski N, Fewer DP, Jokela J. Appl Microbiol Biotechnol. 2010;86:1213–1225. - PMC - PubMed

[4] Sivonen K, Leikoski N, Fewer DP, Jokela J. Appl Microbiol Biotechnol. 2010;86:1213–1225. - PMC - PubMed

[5] Leikoski N, Fewer DP, Sivonen K. Appl Environ Microbiol. 2009;75:853–857. - PMC - PubMed

[6] Leikoski N, Fewer DP, Sivonen K. Appl Environ Microbiol. 2009;75:853–857. - PMC - PubMed

[7] Leikoski N, Fewer DP, Jokela J, Wahlsten M, Rouhiainen L, Sivonen K. Appl Environ Microbiol. 2010;76:701–709. - PMC - PubMed

[8] Leikoski N, Fewer DP, Jokela J, Wahlsten M, Rouhiainen L, Sivonen K. Appl Environ Microbiol. 2010;76:701–709. - PMC - PubMed

[9] Leikoski N, Liu L, Jokela J, Wahlsten M, Gugger M, Calteau A, Permi P, Kerfeld CA, Sivonen K, Fewer DP. Chem Biol. 2013;20:1033–1043. - PubMed

[10] Leikoski N, Liu L, Jokela J, Wahlsten M, Gugger M, Calteau A, Permi P, Kerfeld CA, Sivonen K, Fewer DP. Chem Biol. 2013;20:1033–1043. - PubMed

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A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway

Affiliations

A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway

Authors

Affiliations

Erratum in

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases

Research Materials

Miscellaneous