DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structure and specificity of a permissive bacterial C-prenyltransferase

Abstract

This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. In this work, PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including daptomycin. Two additional PTs also produced novel prenylated daptomycins with improved antibacterial activities over the parent drug.

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [1];  [2];  [1];  [1]
  1. Univ. of Kentucky, Lexington, KY (United States)
  2. Rice Univ., Houston, TX (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); National Center for Advancing Translational Sciences (NCATS); Merck; USDOE Office of Science (SC); Eli Lilly and Company
OSTI Identifier:
1356427
Grant/Contract Number:  
R37 AI52188; R01 CA203257; U01 GM098248; UL1TR001998; AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 13; Journal Issue: 4; Journal ID: ISSN 1552-4450
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biocatalysis; Biosynthesis; Enzymes; X-ray crystallography

Citation Formats

Elshahawi, Sherif I., Cao, Hongnan, Shaaban, Khaled A., Ponomareva, Larissa V., Subramanian, Thangaiah, Farman, Mark L., Spielmann, H. Peter, Phillips Jr., George N., Thorson, Jon S., and Singh, Shanteri. Structure and specificity of a permissive bacterial C-prenyltransferase. United States: N. p., 2017. Web. doi:10.1038/nchembio.2285.
Elshahawi, Sherif I., Cao, Hongnan, Shaaban, Khaled A., Ponomareva, Larissa V., Subramanian, Thangaiah, Farman, Mark L., Spielmann, H. Peter, Phillips Jr., George N., Thorson, Jon S., & Singh, Shanteri. Structure and specificity of a permissive bacterial C-prenyltransferase. United States. https://doi.org/10.1038/nchembio.2285
Elshahawi, Sherif I., Cao, Hongnan, Shaaban, Khaled A., Ponomareva, Larissa V., Subramanian, Thangaiah, Farman, Mark L., Spielmann, H. Peter, Phillips Jr., George N., Thorson, Jon S., and Singh, Shanteri. Mon . "Structure and specificity of a permissive bacterial C-prenyltransferase". United States. https://doi.org/10.1038/nchembio.2285. https://www.osti.gov/servlets/purl/1356427.
@article{osti_1356427,
title = {Structure and specificity of a permissive bacterial C-prenyltransferase},
author = {Elshahawi, Sherif I. and Cao, Hongnan and Shaaban, Khaled A. and Ponomareva, Larissa V. and Subramanian, Thangaiah and Farman, Mark L. and Spielmann, H. Peter and Phillips Jr., George N. and Thorson, Jon S. and Singh, Shanteri},
abstractNote = {This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. In this work, PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including daptomycin. Two additional PTs also produced novel prenylated daptomycins with improved antibacterial activities over the parent drug.},
doi = {10.1038/nchembio.2285},
journal = {Nature Chemical Biology},
number = 4,
volume = 13,
place = {United States},
year = {Mon Feb 06 00:00:00 EST 2017},
month = {Mon Feb 06 00:00:00 EST 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 34 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products
journal, June 2005

  • Kuzuyama, Tomohisa; Noel, Joseph P.; Richard, Stéphane B.
  • Nature, Vol. 435, Issue 7044
  • DOI: 10.1038/nature03668

Tyrosine O -Prenyltransferase SirD Catalyzes S -, C -, and N -Prenylations on Tyrosine and Tryptophan Derivatives
journal, October 2013

  • Rudolf, Jeffrey D.; Poulter, C. Dale
  • ACS Chemical Biology, Vol. 8, Issue 12
  • DOI: 10.1021/cb400691z

Daptomycin: From the Mountain to the Clinic, with Essential Help from Francis Tally, MD
journal, January 2010

  • Eisenstein, Barry I.; Oleson, Jr., Frederick B.; Baltz, Richard H.
  • Clinical Infectious Diseases, Vol. 50, Issue s1
  • DOI: 10.1086/647938

Small molecules from the human microbiota
journal, July 2015


A chemocentric view of the natural product inventory
journal, August 2015


Directed Library of Anilinogeranyl Analogues of Farnesyl Diphosphate via Mixed Solid- and Solution-Phase Synthesis
journal, May 2005

  • Subramanian, Thangaiah; Wang, Zhongwen; Troutman, Jerry M.
  • Organic Letters, Vol. 7, Issue 11
  • DOI: 10.1021/ol050386o

Cytotoxic Indolocarbazoles from Actinomadura melliaura ATCC 39691
journal, June 2015


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Photoaffinity Analogues of Farnesyl Pyrophosphate Transferable by Protein Farnesyl Transferase
journal, July 2002

  • Chehade, Kareem A. H.; Kiegiel, Katarzyna; Isaacs, Richard J.
  • Journal of the American Chemical Society, Vol. 124, Issue 28
  • DOI: 10.1021/ja0124717

Boronated tartrolon antibiotic produced by symbiotic cellulose-degrading bacteria in shipworm gills
journal, January 2013

  • Elshahawi, Sherif I.; Trindade-Silva, Amaro E.; Hanora, Amro
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 4
  • DOI: 10.1073/pnas.1213892110

Multisite Prenylation of 4-Substituted Tryptophans by Dimethylallyltryptophan Synthase
journal, January 2013

  • Rudolf, Jeffrey D.; Wang, Hong; Poulter, C. Dale
  • Journal of the American Chemical Society, Vol. 135, Issue 5
  • DOI: 10.1021/ja310734n

Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules
journal, January 2011

  • Gantt, Richard W.; Peltier-Pain, Pauline; Thorson, Jon S.
  • Natural Product Reports, Vol. 28, Issue 11
  • DOI: 10.1039/c1np00045d

Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C–H Borylation
journal, August 2015

  • Feng, Yu; Holte, Dane; Zoller, Jochen
  • Journal of the American Chemical Society, Vol. 137, Issue 32
  • DOI: 10.1021/jacs.5b07154

Protein Farnesyltransferase-Catalyzed Isoprenoid Transfer to Peptide Depends on Lipid Size and Shape, not Hydrophobicity
journal, November 2008

  • Subramanian, Thangaiah; Liu, Suxia; Troutman, Jerry M.
  • ChemBioChem, Vol. 9, Issue 17
  • DOI: 10.1002/cbic.200800248

Terfestatins B and C, New p -Terphenyl Glycosides Produced by Streptomyces sp. RM-5–8
journal, May 2015


Potential Rearrangements in the Reaction Catalyzed by the Indole Prenyltransferase FtmPT1
journal, September 2013


Enzymatic and chemical modifications of lipopeptide antibiotic A21978C: The synthesis and evaluation of daptomycin (LY146032).
journal, January 1988


Protein promiscuity and its implications for biotechnology
journal, February 2009

  • Nobeli, Irene; Favia, Angelo D.; Thornton, Janet M.
  • Nature Biotechnology, Vol. 27, Issue 2
  • DOI: 10.1038/nbt1519

Microtermolides A and B from Termite-Associated Streptomyces sp. and Structural Revision of Vinylamycin
journal, May 2012

  • Carr, Gavin; Poulsen, Michael; Klassen, Jonathan L.
  • Organic Letters, Vol. 14, Issue 11
  • DOI: 10.1021/ol301043p

A new antibiotic kills pathogens without detectable resistance
journal, January 2015

  • Ling, Losee L.; Schneider, Tanja; Peoples, Aaron J.
  • Nature, Vol. 517, Issue 7535
  • DOI: 10.1038/nature14098

Biocatalysts for Natural Product Biosynthesis
journal, June 2014


Expanding the promiscuity of a natural-product glycosyltransferase by directed evolution
journal, September 2007

  • Williams, Gavin J.; Zhang, Changsheng; Thorson, Jon S.
  • Nature Chemical Biology, Vol. 3, Issue 10
  • DOI: 10.1038/nchembio.2007.28

Manipulation of prenylation reactions by structure-based engineering of bacterial indolactam prenyltransferases
journal, March 2016

  • Mori, Takahiro; Zhang, Lihan; Awakawa, Takayoshi
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms10849

Impacts and perspectives of prenyltransferases of the DMATS superfamily for use in biotechnology
journal, July 2015

  • Fan, Aili; Winkelblech, Julia; Li, Shu-Ming
  • Applied Microbiology and Biotechnology, Vol. 99, Issue 18
  • DOI: 10.1007/s00253-015-6813-9

Evolutionary Relationships of Microbial Aromatic Prenyltransferases
journal, November 2011


Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen
journal, August 2020

  • Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe
  • JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6
  • DOI: 10.1007/s00775-020-01814-y

PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019


Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021


Fine-scale population structure and evidence for local adaptation in Australian giant black tiger shrimp (Penaeus monodon) using SNP analysis
journal, September 2020


PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.45787

Potential Rearrangements in the Reaction Catalyzed by the Indole Prenyltransferase FtmPT1
journal, September 2013


Cytotoxic Indolocarbazoles from Actinomadura melliaura ATCC 39691
journal, June 2015


Terfestatins B and C, New p -Terphenyl Glycosides Produced by Streptomyces sp. RM-5–8
journal, May 2015


Multisite Prenylation of 4-Substituted Tryptophans by Dimethylallyltryptophan Synthase
journal, January 2013

  • Rudolf, Jeffrey D.; Wang, Hong; Poulter, C. Dale
  • Journal of the American Chemical Society, Vol. 135, Issue 5
  • DOI: 10.1021/ja310734n

Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C–H Borylation
journal, August 2015

  • Feng, Yu; Holte, Dane; Zoller, Jochen
  • Journal of the American Chemical Society, Vol. 137, Issue 32
  • DOI: 10.1021/jacs.5b07154

Directed Library of Anilinogeranyl Analogues of Farnesyl Diphosphate via Mixed Solid- and Solution-Phase Synthesis
journal, May 2005

  • Subramanian, Thangaiah; Wang, Zhongwen; Troutman, Jerry M.
  • Organic Letters, Vol. 7, Issue 11
  • DOI: 10.1021/ol050386o

Microtermolides A and B from Termite-Associated Streptomyces sp. and Structural Revision of Vinylamycin
journal, May 2012

  • Carr, Gavin; Poulsen, Michael; Klassen, Jonathan L.
  • Organic Letters, Vol. 14, Issue 11
  • DOI: 10.1021/ol301043p

Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules
journal, January 2011

  • Gantt, Richard W.; Peltier-Pain, Pauline; Thorson, Jon S.
  • Natural Product Reports, Vol. 28, Issue 11
  • DOI: 10.1039/c1np00045d

Mechanistic studies on the indole prenyltransferases
journal, January 2015


MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/s0907444909042073

XDS
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
  • DOI: 10.1107/s0907444909047337

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/s0907444910007493

Biochemical Characterization of a Novel Indole Prenyltransferase from Streptomyces sp. SN-593
journal, March 2010

  • Takahashi, S.; Takagi, H.; Toyoda, A.
  • Journal of Bacteriology, Vol. 192, Issue 11
  • DOI: 10.1128/jb.01557-09

Biocatalysts for Natural Product Biosynthesis
journal, June 2014


Evolutionary Relationships of Microbial Aromatic Prenyltransferases
journal, November 2011


PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.45787

Enzymatic and chemical modifications of lipopeptide antibiotic A21978C: The synthesis and evaluation of daptomycin (LY146032).
journal, January 1988


Works referencing / citing this record:

Molecular Insight into the Mg 2+ -Dependent Allosteric Control of Indole Prenylation by Aromatic Prenyltransferase AmbP1
journal, May 2018

  • Awakawa, Takayoshi; Mori, Takahiro; Nakashima, Yu
  • Angewandte Chemie, Vol. 130, Issue 23
  • DOI: 10.1002/ange.201800855

Two Distinct Substrate Binding Modes for the Normal and Reverse Prenylation of Hapalindoles by the Prenyltransferase AmbP3
journal, December 2017

  • Wong, Chin Piow; Awakawa, Takayoshi; Nakashima, Yu
  • Angewandte Chemie International Edition, Vol. 57, Issue 2
  • DOI: 10.1002/anie.201710682

Molecular Insight into the Mg 2+ -Dependent Allosteric Control of Indole Prenylation by Aromatic Prenyltransferase AmbP1
journal, May 2018

  • Awakawa, Takayoshi; Mori, Takahiro; Nakashima, Yu
  • Angewandte Chemie International Edition, Vol. 57, Issue 23
  • DOI: 10.1002/anie.201800855

Determination of Alkyl-Donor Promiscuity of Tyrosine- O -Prenyltransferase SirD from Leptosphaeria maculans
journal, October 2017

  • Bandari, Chandrasekhar; Scull, Erin M.; Masterson, Johanna M.
  • ChemBioChem, Vol. 18, Issue 23
  • DOI: 10.1002/cbic.201700469

Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production
journal, June 2019


Self-association of a highly charged arginine-rich cell-penetrating peptide
journal, October 2017

  • Tesei, Giulio; Vazdar, Mario; Jensen, Malene Ringkjøbing
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 43
  • DOI: 10.1073/pnas.1712078114

A pharmaceutical model for the molecular evolution of microbial natural products
journal, November 2019

  • Fewer, David P.; Metsä‐Ketelä, Mikko
  • The FEBS Journal, Vol. 287, Issue 7
  • DOI: 10.1111/febs.15129

Biocatalysis for terpene-based polymers
journal, February 2019

  • Farhat, Wissam; Stamm, Arne; Robert-Monpate, Maxime
  • Zeitschrift für Naturforschung C, Vol. 74, Issue 3-4
  • DOI: 10.1515/znc-2018-0199

Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452
journal, April 2018

  • Zhong, Wei-Mao; Wang, Jun-Feng; Shi, Xue-Feng
  • Marine Drugs, Vol. 16, Issue 4
  • DOI: 10.3390/md16040136

Two Distinct Substrate Binding Modes for the Normal and Reverse Prenylation of Hapalindoles by the Prenyltransferase AmbP3
journal, December 2017

  • Wong, Chin Piow; Awakawa, Takayoshi; Nakashima, Yu
  • Angewandte Chemie, Vol. 130, Issue 2
  • DOI: 10.1002/ange.201710682

Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452
journal, April 2018

  • Zhong, Wei-Mao; Wang, Jun-Feng; Shi, Xue-Feng
  • Marine Drugs, Vol. 16, Issue 4
  • DOI: 10.3390/md16040136