Paradigm Shift for Radical S -Adenosyl- l -methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis

doi:10.1021/jacs.8b04061

Title: Paradigm Shift for Radical S -Adenosyl- l -methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis

Abstract

Radical S-adenosyl-L-methionine (SAM) enzymes comprise a vast superfamily catalyzing diverse reactions essential to all life through homolytic SAM cleavage to liberate the highly reactive 5'-deoxyadenosyl radical (5'-dAdo·). Our recent observation of a catalytically competent organometallic intermediate Ω that forms during reaction of the radical SAM (RS) enzyme pyruvate formate-lyase activating-enzyme (PFL-AE) was therefore quite surprising, and led to the question of its broad relevance in the superfamily. We now show that Ω in PFL-AE forms as an intermediate under a variety of mixing order conditions, suggesting it is central to catalysis in this enzyme. We further demonstrate that Ω forms in a suite of RS enzymes chosen to span the totality of superfamily reaction types, implicating Ω as essential in catalysis across the RS superfamily. Finally, EPR and electron nuclear double resonance spectroscopy establish that Ω involves an Fe-C5' bond between 5'-dAdo· and the [4Fe-4S] cluster. An analogous organometallic bond is found in the well-known adenosylcobalamin (coenzyme B₁₂) cofactor used to initiate radical reactions via a 5'- dAdo· intermediate. Liberation of a reactive 5'-dAdo· intermediate via homolytic metal-carbon bond cleavage thus appears to be similar for Ω and coenzyme B₁₂. However, coenzyme B₁₂ is involved in enzymes catalyzing only amore »« less

Authors:

Byer, Amanda S. ^[1]; Yang, Hao ^[2]; McDaniel, Elizabeth C. ^[1]; Kathiresan, Venkatesan ^[2]; Impano, Stella ^[1]; Pagnier, Adrien ^[1]; Watts, Hope ^[1]; Denler, Carly ^[1]; Vagstad, Anna L. ^[3]; Piel, Jörn ^[3]; Duschene, Kaitlin S. ^[1]; Shepard, Eric M. ^[1]; Shields, Thomas P. ^[4]; Scott, Lincoln G. ^[4]; Lilla, Edward A. ^[5];

^[5]; Broderick, William E. ^[1];

^[2];

^[1]

Department of Chemistry &, Biochemistry, Montana State University, Bozeman, Montana 59717, United States
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
Institute of Microbiology, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 4, Zürich 8093, Switzerland
Cassia, LLC, 3030 Bunker Hill Street, Ste. 214, San Diego, California 92109, United States
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, United States

Publication Date:: 2018-06-28

Research Org.:: Montana State Univ., Bozeman, MT (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:: 1459248

Alternate Identifier(s):: OSTI ID: 1508581

Grant/Contract Number:: SC0005404

Resource Type:: Published Article

Journal Name:: Journal of the American Chemical Society

Additional Journal Information:: Journal Name: Journal of the American Chemical Society Journal Volume: 140 Journal Issue: 28; Journal ID: ISSN 0002-7863

Publisher:: American Chemical Society

Country of Publication:: United States

Language:: English

Subject:: 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats


                    Byer, Amanda S., Yang, Hao, McDaniel, Elizabeth C., Kathiresan, Venkatesan, Impano, Stella, Pagnier, Adrien, Watts, Hope, Denler, Carly, Vagstad, Anna L., Piel, Jörn, Duschene, Kaitlin S., Shepard, Eric M., Shields, Thomas P., Scott, Lincoln G., Lilla, Edward A., Yokoyama, Kenichi, Broderick, William E., Hoffman, Brian M., and Broderick, Joan B. Paradigm Shift for Radical S -Adenosyl- l -methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis.  United States: N. p., 2018. 
        Web.  doi:10.1021/jacs.8b04061.

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                    Byer, Amanda S., Yang, Hao, McDaniel, Elizabeth C., Kathiresan, Venkatesan, Impano, Stella, Pagnier, Adrien, Watts, Hope, Denler, Carly, Vagstad, Anna L., Piel, Jörn, Duschene, Kaitlin S., Shepard, Eric M., Shields, Thomas P., Scott, Lincoln G., Lilla, Edward A., Yokoyama, Kenichi, Broderick, William E., Hoffman, Brian M., & Broderick, Joan B. Paradigm Shift for Radical S -Adenosyl- l -methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis.  United States.  doi:10.1021/jacs.8b04061.

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                    Byer, Amanda S., Yang, Hao, McDaniel, Elizabeth C., Kathiresan, Venkatesan, Impano, Stella, Pagnier, Adrien, Watts, Hope, Denler, Carly, Vagstad, Anna L., Piel, Jörn, Duschene, Kaitlin S., Shepard, Eric M., Shields, Thomas P., Scott, Lincoln G., Lilla, Edward A., Yokoyama, Kenichi, Broderick, William E., Hoffman, Brian M., and Broderick, Joan B. Thu .  
        "Paradigm Shift for Radical S -Adenosyl- l -methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis".  United States.  doi:10.1021/jacs.8b04061.

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@article{osti_1459248,

  title        = {Paradigm Shift for Radical S -Adenosyl- l -methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis},

  author       = {Byer, Amanda S. and Yang, Hao and McDaniel, Elizabeth C. and Kathiresan, Venkatesan and Impano, Stella and Pagnier, Adrien and Watts, Hope and Denler, Carly and Vagstad, Anna L. and Piel, Jörn and Duschene, Kaitlin S. and Shepard, Eric M. and Shields, Thomas P. and Scott, Lincoln G. and Lilla, Edward A. and Yokoyama, Kenichi and Broderick, William E. and Hoffman, Brian M. and Broderick, Joan B.},

  abstractNote = {Radical S-adenosyl-L-methionine (SAM) enzymes comprise a vast superfamily catalyzing diverse reactions essential to all life through homolytic SAM cleavage to liberate the highly reactive 5'-deoxyadenosyl radical (5'-dAdo·). Our recent observation of a catalytically competent organometallic intermediate Ω that forms during reaction of the radical SAM (RS) enzyme pyruvate formate-lyase activating-enzyme (PFL-AE) was therefore quite surprising, and led to the question of its broad relevance in the superfamily. We now show that Ω in PFL-AE forms as an intermediate under a variety of mixing order conditions, suggesting it is central to catalysis in this enzyme. We further demonstrate that Ω forms in a suite of RS enzymes chosen to span the totality of superfamily reaction types, implicating Ω as essential in catalysis across the RS superfamily. Finally, EPR and electron nuclear double resonance spectroscopy establish that Ω involves an Fe-C5' bond between 5'-dAdo· and the [4Fe-4S] cluster. An analogous organometallic bond is found in the well-known adenosylcobalamin (coenzyme B12) cofactor used to initiate radical reactions via a 5'- dAdo· intermediate. Liberation of a reactive 5'-dAdo· intermediate via homolytic metal-carbon bond cleavage thus appears to be similar for Ω and coenzyme B12. However, coenzyme B12 is involved in enzymes catalyzing only a small number (~12) of distinct reactions, whereas the RS superfamily has more than 100 000 distinct sequences and over 80 reaction types characterized to date. The appearance of Ω across the RS superfamily therefore dramatically enlarges the sphere of bio-organometallic chemistry in Nature.},

  doi          = {10.1021/jacs.8b04061},

  journal      = {Journal of the American Chemical Society},

  number       = 28,

  volume       = 140,

  place        = {United States},

  year         = {2018},

  month        = {6}

}

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DOI: 10.1021/jacs.8b04061

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Cited by: 9 works

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Figures / Tables:

Figure 1.: Top, premixed (PFL + SAM), RFQ with PFL-AE. Middle, (PFL-AE + SAM) RFQ with PFL. Bottom, (PFL-AE + PFL) + SAM; the slight increase in g_|| suggests a slightly different conformation of Ω. Feature to low field of Ω signal in bottom spectrum due to Cu²⁺ contamination frommore »

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Works referencing / citing this record:

Radical S-adenosylmethionine maquette chemistry: Cx3Cx2C peptide coordinated redox active [4Fe–4S] clusters
journal, September 2019

Galambas, Amanda; Miller, Jacquelyn; Jones, Morgan
JBIC Journal of Biological Inorganic Chemistry, Vol. 24, Issue 6
DOI: 10.1007/s00775-019-01708-8

The hidden enzymology of bacterial natural product biosynthesis
journal, June 2019

Scott, Thomas A.; Piel, Jörn
Nature Reviews Chemistry, Vol. 3, Issue 7
DOI: 10.1038/s41570-019-0107-1

Radical S-adenosylmethionine maquette chemistry: Cx3Cx2C peptide coordinated redox active [4Fe–4S] clusters
journal, September 2019

Galambas, Amanda; Miller, Jacquelyn; Jones, Morgan
JBIC Journal of Biological Inorganic Chemistry, Vol. 24, Issue 6
DOI: 10.1007/s00775-019-01708-8

The hidden enzymology of bacterial natural product biosynthesis
journal, June 2019

Scott, Thomas A.; Piel, Jörn
Nature Reviews Chemistry, Vol. 3, Issue 7
DOI: 10.1038/s41570-019-0107-1

Introduction of d -Amino Acids in Minimalistic Peptide Substrates by an S -Adenosyl- l -Methionine Radical Epimerase
journal, January 2019

Vagstad, Anna L.; Kuranaga, Takefumi; Püntener, Salome
Angewandte Chemie, Vol. 131, Issue 8
DOI: 10.1002/ange.201809508

Introduction of d -Amino Acids in Minimalistic Peptide Substrates by an S -Adenosyl- l -Methionine Radical Epimerase
journal, January 2019

Vagstad, Anna L.; Kuranaga, Takefumi; Püntener, Salome
Angewandte Chemie International Edition, Vol. 58, Issue 8
DOI: 10.1002/anie.201809508

Radical SAM-dependent adenosylation catalyzed by l -tyrosine lyases
journal, January 2019

Wu, Yujie; Wu, Runze; Mandalapu, Dhanaraju
Organic & Biomolecular Chemistry, Vol. 17, Issue 7
DOI: 10.1039/c8ob02906g

Figures / Tables found in this record:

Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.

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Similar Records

Title: Paradigm Shift for Radical S -Adenosyl- l -methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis

Abstract

Citation Formats

Figures / Tables:

Radical S-adenosylmethionine maquette chemistry: Cx3Cx2C peptide coordinated redox active [4Fe–4S] clusters journal, September 2019

The hidden enzymology of bacterial natural product biosynthesis journal, June 2019

Radical S-adenosylmethionine maquette chemistry: Cx3Cx2C peptide coordinated redox active [4Fe–4S] clusters journal, September 2019

The hidden enzymology of bacterial natural product biosynthesis journal, June 2019

Introduction of d -Amino Acids in Minimalistic Peptide Substrates by an S -Adenosyl- l -Methionine Radical Epimerase journal, January 2019

Introduction of d -Amino Acids in Minimalistic Peptide Substrates by an S -Adenosyl- l -Methionine Radical Epimerase journal, January 2019

Radical SAM-dependent adenosylation catalyzed by l -tyrosine lyases journal, January 2019

Radical S-adenosylmethionine maquette chemistry: Cx3Cx2C peptide coordinated redox active [4Fe–4S] clusters
journal, September 2019

The hidden enzymology of bacterial natural product biosynthesis
journal, June 2019

Radical S-adenosylmethionine maquette chemistry: Cx3Cx2C peptide coordinated redox active [4Fe–4S] clusters
journal, September 2019

The hidden enzymology of bacterial natural product biosynthesis
journal, June 2019

Introduction of d -Amino Acids in Minimalistic Peptide Substrates by an S -Adenosyl- l -Methionine Radical Epimerase
journal, January 2019

Introduction of d -Amino Acids in Minimalistic Peptide Substrates by an S -Adenosyl- l -Methionine Radical Epimerase
journal, January 2019

Radical SAM-dependent adenosylation catalyzed by l -tyrosine lyases
journal, January 2019