The crystal structure of DynF from the dynemicin-biosynthesis pathway of Micromonospora chersina

Abigael J. Kosgei; Mitchell D. Miller; Minakshi Bhardwaj; Weijun Xu; Jon S. Thorson; Steven G. Van Lanen; George N. Phillips

doi:10.1107/S2053230X21012322

The crystal structure of DynF from the dynemicin-biosynthesis pathway of Micromonospora chersina

Abigael J. Kosgei, Mitchell D. Miller, Minakshi Bhardwaj, Weijun Xu, Jon S. Thorson, Steven G. Van Lanen, George N. Phillips

Research output: Contribution to journal › Article › peer-review

Abstract

Dynemicin is an enediyne natural product from Micromonospora chersina ATCC53710. Access to the biosynthetic gene cluster of dynemicin has enabled the in vitro study of gene products within the cluster to decipher their roles in assembling this unique molecule. This paper reports the crystal structure of DynF, the gene product of one of the genes within the biosynthetic gene cluster of dynemicin. DynF is revealed to be a dimeric eight-stranded β-barrel structure with palmitic acid bound within a cavity. The presence of palmitic acid suggests that DynF may be involved in binding the precursor polyene heptaene, which is central to the synthesis of the ten-membered ring of the enediyne core.

Original language	English
Pages (from-to)	1-7
Number of pages	7
Journal	Acta Crystallographica Section F:Structural Biology Communications
Volume	78
DOIs	https://doi.org/10.1107/S2053230X21012322
State	Published - Jan 1 2022

Bibliographical note

Funding Information:
This research was funded by National Institutes of Health grant R01 GM115261 (JST and GNP), National Cancer Institute grant R01 CA217255 (JST, SGVL and GNP) and National Science Foundation, BioXFEL Science and Technology Center grant No. 1231306 (GNP).

Funding Information:
This work used research resources provided by the Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation (CPRI; NIH P20 GM130456), the University of Kentucky College of Pharmacy and the National Center for Advancing Translational Sciences (UL1TR000117 and UL1TR001998). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. GM/CA@APS has been funded by the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006, P30GM138396). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National institutes of Health or the National Science Foundation.

Publisher Copyright:
© 2022 International Union of Crystallography. All rights reserved.

Keywords

Anthraquinone
Biosynthetic gene clusters
Dynemicin
Enediynes
Micromonospora chersina ATCC53710
Natural products
Polyketides
Unknown function
β-barrel

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Genetics
Condensed Matter Physics

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10.1107/S2053230X21012322

Cite this

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title = "The crystal structure of DynF from the dynemicin-biosynthesis pathway of Micromonospora chersina",

abstract = "Dynemicin is an enediyne natural product from Micromonospora chersina ATCC53710. Access to the biosynthetic gene cluster of dynemicin has enabled the in vitro study of gene products within the cluster to decipher their roles in assembling this unique molecule. This paper reports the crystal structure of DynF, the gene product of one of the genes within the biosynthetic gene cluster of dynemicin. DynF is revealed to be a dimeric eight-stranded β-barrel structure with palmitic acid bound within a cavity. The presence of palmitic acid suggests that DynF may be involved in binding the precursor polyene heptaene, which is central to the synthesis of the ten-membered ring of the enediyne core.",

keywords = "Anthraquinone, Biosynthetic gene clusters, Dynemicin, Enediynes, Micromonospora chersina ATCC53710, Natural products, Polyketides, Unknown function, β-barrel",

author = "Kosgei, {Abigael J.} and Miller, {Mitchell D.} and Minakshi Bhardwaj and Weijun Xu and Thorson, {Jon S.} and {Van Lanen}, {Steven G.} and Phillips, {George N.}",

note = "Funding Information: This research was funded by National Institutes of Health grant R01 GM115261 (JST and GNP), National Cancer Institute grant R01 CA217255 (JST, SGVL and GNP) and National Science Foundation, BioXFEL Science and Technology Center grant No. 1231306 (GNP). Funding Information: This work used research resources provided by the Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation (CPRI; NIH P20 GM130456), the University of Kentucky College of Pharmacy and the National Center for Advancing Translational Sciences (UL1TR000117 and UL1TR001998). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. GM/CA@APS has been funded by the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006, P30GM138396). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National institutes of Health or the National Science Foundation. Publisher Copyright: {\textcopyright} 2022 International Union of Crystallography. All rights reserved.",

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AU - Kosgei, Abigael J.

AU - Miller, Mitchell D.

AU - Bhardwaj, Minakshi

AU - Xu, Weijun

AU - Thorson, Jon S.

AU - Van Lanen, Steven G.

AU - Phillips, George N.

N1 - Funding Information: This research was funded by National Institutes of Health grant R01 GM115261 (JST and GNP), National Cancer Institute grant R01 CA217255 (JST, SGVL and GNP) and National Science Foundation, BioXFEL Science and Technology Center grant No. 1231306 (GNP). Funding Information: This work used research resources provided by the Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation (CPRI; NIH P20 GM130456), the University of Kentucky College of Pharmacy and the National Center for Advancing Translational Sciences (UL1TR000117 and UL1TR001998). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. GM/CA@APS has been funded by the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006, P30GM138396). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National institutes of Health or the National Science Foundation. Publisher Copyright: © 2022 International Union of Crystallography. All rights reserved.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Dynemicin is an enediyne natural product from Micromonospora chersina ATCC53710. Access to the biosynthetic gene cluster of dynemicin has enabled the in vitro study of gene products within the cluster to decipher their roles in assembling this unique molecule. This paper reports the crystal structure of DynF, the gene product of one of the genes within the biosynthetic gene cluster of dynemicin. DynF is revealed to be a dimeric eight-stranded β-barrel structure with palmitic acid bound within a cavity. The presence of palmitic acid suggests that DynF may be involved in binding the precursor polyene heptaene, which is central to the synthesis of the ten-membered ring of the enediyne core.

AB - Dynemicin is an enediyne natural product from Micromonospora chersina ATCC53710. Access to the biosynthetic gene cluster of dynemicin has enabled the in vitro study of gene products within the cluster to decipher their roles in assembling this unique molecule. This paper reports the crystal structure of DynF, the gene product of one of the genes within the biosynthetic gene cluster of dynemicin. DynF is revealed to be a dimeric eight-stranded β-barrel structure with palmitic acid bound within a cavity. The presence of palmitic acid suggests that DynF may be involved in binding the precursor polyene heptaene, which is central to the synthesis of the ten-membered ring of the enediyne core.

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KW - Polyketides

KW - Unknown function

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JF - Acta Crystallographica Section F:Structural Biology Communications

SN - 1744-3091

ER -

The crystal structure of DynF from the dynemicin-biosynthesis pathway of Micromonospora chersina

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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