Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis
Abstract
Enediynes are potent natural product anticancer antibiotics, and are classified as 9- or 10-membered according to the size of their enediyne core carbon skeleton. Both 9- and 10-membered enediyne cores are biosynthesized by the enediyne polyketide synthase (PKSE), thioesterase (TE), and PKSE-associated enzymes. Though the divergence between 9- and 10-membered enediyne core biosynthesis remains unclear, it has been observed that nascent polyketide intermediates, tethered to the acyl carrier protein (ACP) domain of PKSE, could be released by TE in the absence of the PKSE-associated enzymes. Here, we determined the crystal structure of SgcE10, the TE that participates in the biosynthesis of the 9-membered enediyne C-1027. Structural comparison of SgcE10 with CalE7 and DynE7, two TEs that participate in the biosynthesis of the 10-membered enediynes calicheamicin and dynemicin, respectively, revealed that they share a common α/β hot-dog fold. The amino acids involved in both substrate binding and catalysis are conserved among SgcE10, CalE7, and DynE7. The volume and the shape of the substrate-binding channel and active site in SgcE10, CalE7, and DynE7 confirm that TEs from both 9- and 10-membered enediyne biosynthetic machineries bind the linear form of similar ACP-tethered polyene intermediates. Taken together, our findings further support the proposal thatmore »
- Authors:
-
[5]
- Scripps Research Inst., Jupiter, FL (United States). Dept. of Chemistry
- Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics, Structural Biology Center, Biosciences Division
- Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics
- Rice Univ., Houston, TX (United States). BioSciences at Rice, Dept. of Chemistry
- Scripps Research Inst., Jupiter, FL (United States). Dept. of Chemistry, Dept. of Molecular Medicine, Natural Products Library Initiative
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Arnold and Mabel Beckman Foundation; Scripps Research Institute
- OSTI Identifier:
- 1393895
- Grant/Contract Number:
- AC02-06CH11357; AC02-06CH113; GM098248; CA078747; GM115575
- Resource Type:
- Accepted Manuscript
- Journal Name:
- ACS Omega
- Additional Journal Information:
- Journal Volume: 2; Journal Issue: 8; Journal ID: ISSN 2470-1343
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; bacteria; crystal structure; molecular structure; protein structure; proteins
Citation Formats
Annaval, Thibault, Rudolf, Jeffrey D., Chang, Chin-Yuan, Lohman, Jeremy R., Kim, Youngchang, Bigelow, Lance, Jedrzejczak, Robert, Babnigg, Gyorgy, Joachimiak, Andrzej, Phillips, George N., and Shen, Ben. Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis. United States: N. p., 2017.
Web. doi:10.1021/acsomega.7b00933.
Annaval, Thibault, Rudolf, Jeffrey D., Chang, Chin-Yuan, Lohman, Jeremy R., Kim, Youngchang, Bigelow, Lance, Jedrzejczak, Robert, Babnigg, Gyorgy, Joachimiak, Andrzej, Phillips, George N., & Shen, Ben. Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis. United States. https://doi.org/10.1021/acsomega.7b00933
Annaval, Thibault, Rudolf, Jeffrey D., Chang, Chin-Yuan, Lohman, Jeremy R., Kim, Youngchang, Bigelow, Lance, Jedrzejczak, Robert, Babnigg, Gyorgy, Joachimiak, Andrzej, Phillips, George N., and Shen, Ben. Wed .
"Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis". United States. https://doi.org/10.1021/acsomega.7b00933. https://www.osti.gov/servlets/purl/1393895.
@article{osti_1393895,
title = {Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis},
author = {Annaval, Thibault and Rudolf, Jeffrey D. and Chang, Chin-Yuan and Lohman, Jeremy R. and Kim, Youngchang and Bigelow, Lance and Jedrzejczak, Robert and Babnigg, Gyorgy and Joachimiak, Andrzej and Phillips, George N. and Shen, Ben},
abstractNote = {Enediynes are potent natural product anticancer antibiotics, and are classified as 9- or 10-membered according to the size of their enediyne core carbon skeleton. Both 9- and 10-membered enediyne cores are biosynthesized by the enediyne polyketide synthase (PKSE), thioesterase (TE), and PKSE-associated enzymes. Though the divergence between 9- and 10-membered enediyne core biosynthesis remains unclear, it has been observed that nascent polyketide intermediates, tethered to the acyl carrier protein (ACP) domain of PKSE, could be released by TE in the absence of the PKSE-associated enzymes. Here, we determined the crystal structure of SgcE10, the TE that participates in the biosynthesis of the 9-membered enediyne C-1027. Structural comparison of SgcE10 with CalE7 and DynE7, two TEs that participate in the biosynthesis of the 10-membered enediynes calicheamicin and dynemicin, respectively, revealed that they share a common α/β hot-dog fold. The amino acids involved in both substrate binding and catalysis are conserved among SgcE10, CalE7, and DynE7. The volume and the shape of the substrate-binding channel and active site in SgcE10, CalE7, and DynE7 confirm that TEs from both 9- and 10-membered enediyne biosynthetic machineries bind the linear form of similar ACP-tethered polyene intermediates. Taken together, our findings further support the proposal that the divergence between 9- and 10-membered enediyne core biosynthesis occurs beyond PKSE and TE catalysis.},
doi = {10.1021/acsomega.7b00933},
journal = {ACS Omega},
number = 8,
volume = 2,
place = {United States},
year = {Wed Aug 30 00:00:00 EDT 2017},
month = {Wed Aug 30 00:00:00 EDT 2017}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 8 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Characterization and phylogenetic analysis of the complete mitochondrial genome of the pathogenic fungus Ilyonectria destructans
journal, February 2022
- Androsiuk, Piotr; Okorski, Adam; Paukszto, Łukasz
- Scientific Reports, Vol. 12, Issue 1
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
The Calicheamicin Gene Cluster and Its Iterative Type I Enediyne PKS
journal, August 2002
- Ahlert, J.
- Science, Vol. 297, Issue 5584
Products of the iterative polyketide synthases in 9- and 10-membered enediyne biosynthesis
journal, January 2009
- Sun, Huihua; Kong, Rong; Zhu, Di
- Chemical Communications, Issue 47
Enediyne Natural Products: Biosynthesis and Prospect Towards Engineering Novel Antitumor Agents
journal, January 2005
- Shen, Ben; Liu, Wen; Nonaka, Koichi
- Frontiers in Medicinal Chemistry - Online, Vol. 2, Issue 1
Structure and Catalytic Mechanism of the Thioesterase CalE7 in Enediyne Biosynthesis
journal, June 2009
- Kotaka, Masayo; Kong, Rong; Qureshi, Insaf
- Journal of Biological Chemistry, Vol. 284, Issue 23
Calculation of protein extinction coefficients from amino acid sequence data
journal, November 1989
- Gill, Stanley C.; von Hippel, Peter H.
- Analytical Biochemistry, Vol. 182, Issue 2
The structures of type I polyketide synthases
journal, January 2012
- Keatinge-Clay, Adrian T.
- Natural Product Reports, Vol. 29, Issue 10
Biosynthesis of Enediyne Antitumor Antibiotics
journal, April 2008
- Van Lanen, Steven; Shen, Ben
- Current Topics in Medicinal Chemistry, Vol. 8, Issue 6
An expression vector tailored for large-scale, high-throughput purification of recombinant proteins
journal, June 2006
- Donnelly, Mark I.; Zhou, Min; Millard, Cynthia Sanville
- Protein Expression and Purification, Vol. 47, Issue 2
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis
journal, January 2008
- Zhang, J.; Van Lanen, S. G.; Ju, J.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 5, p. 1460-1465
Strain Prioritization and Genome Mining for Enediyne Natural Products
journal, December 2016
- Yan, Xiaohui; Ge, Huiming; Huang, Tingting
- mBio, Vol. 7, Issue 6
Identification of a Nonaketide Product for the Iterative Polyketide Synthase in Biosynthesis of the Nine-Membered Enediyne C-1027
journal, September 2010
- Chen, Xiaolei; Guo, Zu-Feng; Lai, Pok Man
- Angewandte Chemie International Edition, Vol. 49, Issue 43
Production of Octaketide Polyenes by the Calicheamicin Polyketide Synthase CalE8: Implications for the Biosynthesis of Enediyne Core Structures
journal, September 2009
- Belecki, Katherine; Crawford, Jason M.; Townsend, Craig A.
- Journal of the American Chemical Society, Vol. 131, Issue 35
Characterization of the Maduropeptin Biosynthetic Gene Cluster from Actinomadura madurae ATCC 39144 Supporting a Unifying Paradigm for Enediyne Biosynthesis
journal, October 2007
- Van Lanen, Steven G.; Oh, Tae-jin; Liu, Wen
- Journal of the American Chemical Society, Vol. 129, Issue 43
Mechanism and specificity of the terminal thioesterase domain from the erythromycin polyketide synthase
journal, February 1999
- Gokhale, Rajesh S.; Hunziker, Daniel; Cane, David E.
- Chemistry & Biology, Vol. 6, Issue 2
Ligation-independent cloning of PCR products (LIC-PCR)
journal, January 1990
- Aslanidis, Charalampos; de Jong, Pieter J.
- Nucleic Acids Research, Vol. 18, Issue 20
Chemistry and Biology of the Enediyne Anticancer Antibiotics
journal, November 1991
- Nicolaou, K. C.; Dai, W. -M.
- Angewandte Chemie International Edition in English, Vol. 30, Issue 11
Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery
journal, August 2015
- Rudolf, Jeffrey D.; Yan, Xiaohui; Shen, Ben
- Journal of Industrial Microbiology & Biotechnology, Vol. 43, Issue 2-3
Complexity and simplicity in the biosynthesis of enediyne natural products
journal, January 2010
- Liang, Zhao-Xun
- Natural Product Reports, Vol. 27, Issue 4
Enediyne Natural Products: Biosynthesis and Prospect Towards Engineering Novel Antitumor Agents
journal, November 2003
- Shen, Ben; Liu, Wen; Nonaka, Koichi
- Current Medicinal Chemistry, Vol. 10, Issue 21
Characterization of the Maduropeptin Biosynthetic Gene Cluster from Actinomadura madurae ATCC 39144 Supporting a Unifying Paradigm for Enediyne Biosynthesis
journal, October 2007
- Van Lanen, Steven G.; Oh, Tae-jin; Liu, Wen
- Journal of the American Chemical Society, Vol. 129, Issue 43
Chemistry and Biology of the Enediyne Anticancer Antibiotics
journal, November 1991
- Nicolaou, K. C.; Dai, W. -M.
- Angewandte Chemie International Edition in English, Vol. 30, Issue 11
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis
journal, January 2008
- Zhang, J.; Van Lanen, S. G.; Ju, J.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 5, p. 1460-1465
Complexity and simplicity in the biosynthesis of enediyne natural products
journal, January 2010
- Liang, Zhao-Xun
- Natural Product Reports, Vol. 27, Issue 4
Biosynthesis of Enediyne Antitumor Antibiotics
journal, April 2008
- Van Lanen, Steven; Shen, Ben
- Current Topics in Medicinal Chemistry, Vol. 8, Issue 6
Iterative type I polyketide synthases involved in enediyne natural product biosynthesis
journal, September 2014
- Chen, Xiaolei; Ji, Rui; Jiang, Xin
- IUBMB Life, Vol. 66, Issue 9
Characterization of a Carbonyl-Conjugated Polyene Precursor in 10-Membered Enediyne Biosynthesis
journal, July 2008
- Kong, Rong; Goh, Lan Pei; Liew, Chong Wai
- Journal of the American Chemical Society, Vol. 130, Issue 26
Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes
journal, June 2010
- Horsman, G. P.; Chen, Y.; Thorson, J. S.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 25
Identification of a Nonaketide Product for the Iterative Polyketide Synthase in Biosynthesis of the Nine-Membered Enediyne C-1027
journal, September 2010
- Chen, Xiaolei; Guo, Zu-Feng; Lai, Pok Man
- Angewandte Chemie International Edition, Vol. 49, Issue 43
Production of Octaketide Polyenes by the Calicheamicin Polyketide Synthase CalE8: Implications for the Biosynthesis of Enediyne Core Structures
journal, September 2009
- Belecki, Katherine; Crawford, Jason M.; Townsend, Craig A.
- Journal of the American Chemical Society, Vol. 131, Issue 35
Products of the iterative polyketide synthases in 9- and 10-membered enediyne biosynthesis
journal, January 2009
- Sun, Huihua; Kong, Rong; Zhu, Di
- Chemical Communications, Issue 47
Induced-fit upon Ligand Binding Revealed by Crystal Structures of the Hot-dog Fold Thioesterase in Dynemicin Biosynthesis
journal, November 2010
- Liew, Chong Wai; Sharff, Andrew; Kotaka, Masayo
- Journal of Molecular Biology, Vol. 404, Issue 2
Role of type II thioesterases: evidence for removal of short acyl chains produced by aberrant decarboxylation of chain extender units
journal, February 2001
- Heathcote, Michelle L.; Staunton, James; Leadlay, Peter F.
- Chemistry & Biology, Vol. 8, Issue 2, p. 207-220
Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: Versatility from a unique substrate channel
journal, December 2001
- Tsai, S. -C.; Miercke, L. J. W.; Krucinski, J.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 26
The structures of type I polyketide synthases
journal, January 2012
- Keatinge-Clay, Adrian T.
- Natural Product Reports, Vol. 29, Issue 10
Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery
journal, August 2015
- Rudolf, Jeffrey D.; Yan, Xiaohui; Shen, Ben
- Journal of Industrial Microbiology & Biotechnology, Vol. 43, Issue 2-3
Automation of protein purification for structural genomics
journal, March 2004
- Kim, Youngchang; Dementieva, Irina; Zhou, Min
- Journal of Structural and Functional Genomics, Vol. 5, Issue 1/2
Biosynthesis of the Enediyne Antitumor Antibiotic C-1027
journal, August 2002
- Liu, W.
- Science, Vol. 297, Issue 5584
The Calicheamicin Gene Cluster and Its Iterative Type I Enediyne PKS
journal, August 2002
- Ahlert, J.
- Science, Vol. 297, Issue 5584
High-throughput protein purification and quality assessment for crystallization
journal, September 2011
- Kim, Youngchang; Babnigg, Gyorgy; Jedrzejczak, Robert
- Methods, Vol. 55, Issue 1
A Family of LIC Vectors for High-Throughput Cloning and Purification of Proteins
book, January 2009
- Eschenfeldt, William H.; Lucy, Stols; Millard, Cynthia Sanville
- Methods in Molecular Biology
Ligation-independent cloning of PCR products (LIC-PCR)
journal, January 1990
- Aslanidis, Charalampos; de Jong, Pieter J.
- Nucleic Acids Research, Vol. 18, Issue 20
An expression vector tailored for large-scale, high-throughput purification of recombinant proteins
journal, June 2006
- Donnelly, Mark I.; Zhou, Min; Millard, Cynthia Sanville
- Protein Expression and Purification, Vol. 47, Issue 2
Calculation of protein extinction coefficients from amino acid sequence data
journal, November 1989
- Gill, Stanley C.; von Hippel, Peter H.
- Analytical Biochemistry, Vol. 182, Issue 2
The Structural Biology Center 19ID undulator beamline: facility specifications and protein crystallographic results
journal, December 2005
- Rosenbaum, Gerd; Alkire, Randy W.; Evans, Gwyndaf
- Journal of Synchrotron Radiation, Vol. 13, Issue 1
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes
journal, July 2006
- Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8
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
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011
- Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
PROCHECK: a program to check the stereochemical quality of protein structures
journal, April 1993
- Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.
- Journal of Applied Crystallography, Vol. 26, Issue 2
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
MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets
journal, March 2016
- Kumar, Sudhir; Stecher, Glen; Tamura, Koichiro
- Molecular Biology and Evolution, Vol. 33, Issue 7
Works referencing / citing this record:
Acyltransferases as Tools for Polyketide Synthase Engineering
journal, July 2018
- Musiol-Kroll, Ewa; Wohlleben, Wolfgang
- Antibiotics, Vol. 7, Issue 3