Characterization of a Copper-Chelating Natural Product from the MethanotrophMethylosinussp. LW3

Yun Ji Park; Gerri M. Roberts; Rana Montaser; Grace E. Kenney; Paul M. Thomas; Neil L. Kelleher; Amy C. Rosenzweig

doi:10.1021/acs.biochem.1c00443

Characterization of a Copper-Chelating Natural Product from the MethanotrophMethylosinussp. LW3

Yun Ji Park, Gerri M. Roberts, Rana Montaser, Grace E. Kenney, Paul M. Thomas, Neil L. Kelleher, Amy C. Rosenzweig^*

^*Corresponding author for this work

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

8 Scopus citations

Abstract

Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptidic natural products that bind copper with high affinity. Methanotrophic bacteria use Mbns to acquire copper needed for enzymatic methane oxidation. Despite the presence of Mbn operons in a range of methanotroph and other bacterial genomes, few Mbns have been isolated and structurally characterized. Here we report the isolation of a novel Mbn from the methanotrophMethylosinus(Ms.) sp. LW3. Mass spectrometric and nuclear magnetic resonance spectroscopic data indicate that this Mbn, the largest characterized to date, consists of a 13-amino acid backbone modified to include pyrazinedione/oxazolone rings and neighboring thioamide groups derived from cysteine residues. The pyrazinedione ring is more stable to acid hydrolysis than the oxazolone ring and likely protects the Mbn from degradation. The structure corresponds exactly to that predicted on the basis of theMs. sp. LW3 Mbn operon content, providing support for the proposed role of an uncharacterized biosynthetic enzyme, MbnF, and expanding the diversity of known Mbns.

Original language	English (US)
Pages (from-to)	2845-2850
Number of pages	6
Journal	Biochemistry
Volume	60
Issue number	38
DOIs	https://doi.org/10.1021/acs.biochem.1c00443
State	Published - Sep 28 2021

Funding

The authors thank Dr. Ludmila Chistoserdova for providing Ms. sp. LW3 and Dr. Yongbo Zhang at the Integrated Molecular Structure Education and Research Center (IMSERC) at Northwestern University for NMR assistance. NMR spectroscopy and ESI-MS were performed at IMSERC and the Proteomics Center of Excellence. NMR spectroscopy is supported by the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [National Science Foundation (NSF) Grant ECCS-2025633], National Institutes of Health Grant 1S10OD012016-01/1S10RR019071-01A1, and Northwestern University, and ESI-MS is supported by the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF Grant ECCS-2025633) and Northwestern University. This work was supported by National Institutes of Health Grants R35 GM118035 (A.C.R.), F32 GM131665 (Y.J.P.), and P41 GM108569 (N.L.K.) and a National Science Foundation GRFP (G.M.R.).

ASJC Scopus subject areas

Biochemistry

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title = "Characterization of a Copper-Chelating Natural Product from the MethanotrophMethylosinussp. LW3",

abstract = "Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptidic natural products that bind copper with high affinity. Methanotrophic bacteria use Mbns to acquire copper needed for enzymatic methane oxidation. Despite the presence of Mbn operons in a range of methanotroph and other bacterial genomes, few Mbns have been isolated and structurally characterized. Here we report the isolation of a novel Mbn from the methanotrophMethylosinus(Ms.) sp. LW3. Mass spectrometric and nuclear magnetic resonance spectroscopic data indicate that this Mbn, the largest characterized to date, consists of a 13-amino acid backbone modified to include pyrazinedione/oxazolone rings and neighboring thioamide groups derived from cysteine residues. The pyrazinedione ring is more stable to acid hydrolysis than the oxazolone ring and likely protects the Mbn from degradation. The structure corresponds exactly to that predicted on the basis of theMs. sp. LW3 Mbn operon content, providing support for the proposed role of an uncharacterized biosynthetic enzyme, MbnF, and expanding the diversity of known Mbns.",

author = "Park, {Yun Ji} and Roberts, {Gerri M.} and Rana Montaser and Kenney, {Grace E.} and Thomas, {Paul M.} and Kelleher, {Neil L.} and Rosenzweig, {Amy C.}",

note = "Funding Information: The authors thank Dr. Ludmila Chistoserdova for providing Ms. sp. LW3 and Dr. Yongbo Zhang at the Integrated Molecular Structure Education and Research Center (IMSERC) at Northwestern University for NMR assistance. NMR spectroscopy and ESI-MS were performed at IMSERC and the Proteomics Center of Excellence. NMR spectroscopy is supported by the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [National Science Foundation (NSF) Grant ECCS-2025633], National Institutes of Health Grant 1S10OD012016-01/1S10RR019071-01A1, and Northwestern University, and ESI-MS is supported by the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF Grant ECCS-2025633) and Northwestern University. Funding Information: This work was supported by National Institutes of Health Grants R35 GM118035 (A.C.R.), F32 GM131665 (Y.J.P.), and P41 GM108569 (N.L.K.) and a National Science Foundation GRFP (G.M.R.). Publisher Copyright: {\textcopyright} 2021 American Chemical Society",

year = "2021",

month = sep,

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doi = "10.1021/acs.biochem.1c00443",

language = "English (US)",

volume = "60",

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T1 - Characterization of a Copper-Chelating Natural Product from the MethanotrophMethylosinussp. LW3

AU - Park, Yun Ji

AU - Roberts, Gerri M.

AU - Montaser, Rana

AU - Kenney, Grace E.

AU - Thomas, Paul M.

AU - Kelleher, Neil L.

AU - Rosenzweig, Amy C.

N1 - Funding Information: The authors thank Dr. Ludmila Chistoserdova for providing Ms. sp. LW3 and Dr. Yongbo Zhang at the Integrated Molecular Structure Education and Research Center (IMSERC) at Northwestern University for NMR assistance. NMR spectroscopy and ESI-MS were performed at IMSERC and the Proteomics Center of Excellence. NMR spectroscopy is supported by the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [National Science Foundation (NSF) Grant ECCS-2025633], National Institutes of Health Grant 1S10OD012016-01/1S10RR019071-01A1, and Northwestern University, and ESI-MS is supported by the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF Grant ECCS-2025633) and Northwestern University. Funding Information: This work was supported by National Institutes of Health Grants R35 GM118035 (A.C.R.), F32 GM131665 (Y.J.P.), and P41 GM108569 (N.L.K.) and a National Science Foundation GRFP (G.M.R.). Publisher Copyright: © 2021 American Chemical Society

PY - 2021/9/28

Y1 - 2021/9/28

N2 - Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptidic natural products that bind copper with high affinity. Methanotrophic bacteria use Mbns to acquire copper needed for enzymatic methane oxidation. Despite the presence of Mbn operons in a range of methanotroph and other bacterial genomes, few Mbns have been isolated and structurally characterized. Here we report the isolation of a novel Mbn from the methanotrophMethylosinus(Ms.) sp. LW3. Mass spectrometric and nuclear magnetic resonance spectroscopic data indicate that this Mbn, the largest characterized to date, consists of a 13-amino acid backbone modified to include pyrazinedione/oxazolone rings and neighboring thioamide groups derived from cysteine residues. The pyrazinedione ring is more stable to acid hydrolysis than the oxazolone ring and likely protects the Mbn from degradation. The structure corresponds exactly to that predicted on the basis of theMs. sp. LW3 Mbn operon content, providing support for the proposed role of an uncharacterized biosynthetic enzyme, MbnF, and expanding the diversity of known Mbns.

AB - Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptidic natural products that bind copper with high affinity. Methanotrophic bacteria use Mbns to acquire copper needed for enzymatic methane oxidation. Despite the presence of Mbn operons in a range of methanotroph and other bacterial genomes, few Mbns have been isolated and structurally characterized. Here we report the isolation of a novel Mbn from the methanotrophMethylosinus(Ms.) sp. LW3. Mass spectrometric and nuclear magnetic resonance spectroscopic data indicate that this Mbn, the largest characterized to date, consists of a 13-amino acid backbone modified to include pyrazinedione/oxazolone rings and neighboring thioamide groups derived from cysteine residues. The pyrazinedione ring is more stable to acid hydrolysis than the oxazolone ring and likely protects the Mbn from degradation. The structure corresponds exactly to that predicted on the basis of theMs. sp. LW3 Mbn operon content, providing support for the proposed role of an uncharacterized biosynthetic enzyme, MbnF, and expanding the diversity of known Mbns.

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JO - Biochemistry

JF - Biochemistry

IS - 38

ER -

Characterization of a Copper-Chelating Natural Product from the MethanotrophMethylosinussp. LW3

Abstract

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