Characterization of Methanobactin from <i>Methylosinus</i> sp. LW4

Kenney, Grace E.; Goering, Anthony W.; Ross, Matthew O.; DeHart, Caroline J.; Thomas, Paul M.; Hoffman, Brian M.; Kelleher, Neil L.; Rosenzweig, Amy C.

doi:10.1021/jacs.6b06821

Cited by 35 publications

(50 citation statements)

References 14 publications

(53 reference statements)

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“…The structure of a second Ms. Mbn, Ms. sp. LW4 Mbn, was predicted based on its Mbn operon content; despite an otherwise divergent peptidic backbone, this Mbn has two oxazolone/thioamide pairs, an internal disulfide bond, and an N-terminal ketone group, as observed in Ms. trichosporium OB3b Mbn ( Figure 1B) (24).…”

Section: Mbn Structuresmentioning

confidence: 96%

“…Supporting this notion, the non-copper-chelating nitrogen in heterocycle A in the Mc. Mbn crystal structures appears to be protonated (24). Thioamide/enethiol tautomerization may also occur, depending on ionic state, copper chelation, and the identity of the neighboring heterocycle.…”

Section: Mbn Structuresmentioning

confidence: 98%

“…Oxazolone B absorbs at 340-342 nm, while heterocycle A absorbs at 388-394 nm (22,(24)(25)(26). Fluorescence is observed at 375-475 nm with excitation at heterocycle-associated absorbance maxima (26,27).…”

Section: Mbn Structuresmentioning

confidence: 99%

“…Unmodified cysteines may form disulfide bonds, as in Ms. trichosporium OB3b and Ms. sp. LW4 Mbns (17,24).…”

Section: The Biosynthetic Pathway Of Mbnsmentioning

confidence: 99%

“…This compound was proposed to result from incomplete oxazolone A formation without MbnN. Given that all Mbns characterized thus far have oxazolone B (21,22,24,25), despite the absence of an aminotransferase in all Mc. Mbn operons (19), it is unclear why oxazolone A would require MbnN in the two Ms. species.…”

Section: The Biosynthetic Pathway Of Mbnsmentioning

confidence: 99%

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Methanobactins: Maintaining copper homeostasis in methanotrophs and beyond

Kenney¹,

Rosenzweig

2018

Journal of Biological Chemistry

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Methanobactins (Mbns) are ribosomally produced, post-translationally modified natural products that bind copper with high affinity and specificity. Originally identified in methanotrophic bacteria, which have a high need for copper, operons encoding these compounds have also been found in many non-methanotrophic bacteria. The proteins responsible for Mbn biosynthesis include several novel enzymes. Mbn transport involves export through a multidrug efflux pump and reinternalization via a TonB-dependent transporter. Release of copper from Mbn and the molecular basis for copper regulation of Mbn production remain to be elucidated. Future work is likely to result in the identification of new enzymatic chemistry, opportunities for bioengineering and drug targeting of copper metabolism, and an expanded understanding of microbial metal homeostasis.Transition metals are key cofactors in metabolically important enzymes across all kingdoms of life (1). Nevertheless, careful control of cellular metal levels is required: a cellular surplus can limit viability due to oxidative stress (2), but metal starvation can also be fatal. Investigations of metal influx during conditions of metal scarcity have often been limited to iron, which is poorly bioavailable under aerobic conditions (3). Ironchelating natural products (siderophores) are secreted by many species, and iron from siderophores is incorporated into the cellular iron pool after re-internalization (4). While efflux has historically dominated studies of non-iron homeostasis, there is increasing evidence that similar systems exist for uptake of other metal ions (5, 6).

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Section: Mbn Structuresmentioning

confidence: 96%

Section: Mbn Structuresmentioning

confidence: 98%

Section: Mbn Structuresmentioning

confidence: 99%

“…Unmodified cysteines may form disulfide bonds, as in Ms. trichosporium OB3b and Ms. sp. LW4 Mbns (17,24).…”

Section: The Biosynthetic Pathway Of Mbnsmentioning

confidence: 99%

Section: The Biosynthetic Pathway Of Mbnsmentioning

confidence: 99%

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Methanobactins: Maintaining copper homeostasis in methanotrophs and beyond

Kenney¹,

Rosenzweig

2018

Journal of Biological Chemistry

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Insight into Metal Removal from Peptides that Sequester Copper for Methane Oxidation

Baslé

Ghazouani

Lee

et al. 2018

Chemistry A European J

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Methanobactins (Mbns) are modified peptides that sequester copper (Cu) methanotrophs use to oxidize methane. Limited structural information is available for this class of natural products, as is an understanding of how cells are able to utilize Mbn‐bound Cu. The crystal structure of Methylosinus sporium NR3K CuI–Mbn provides further information about the structural diversity of Mbns and the first insight into their Cu‐release mechanism. Nitrogen ligands from oxazolone and pyrazinediol rings chelate CuI along with adjacent coordinating sulfurs from thioamides. In vitro solution data are consistent with a CuI–Mbn monomer as found for previously characterized Mbns. In the crystal structure, the N‐terminal region has undergone a conformational change allowing the formation of a CuI 2–Mbn2 dimer with CuI sites bound by chelating units from adjacent chains. Such a structural alteration will facilitate CuI release from Mbns.

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The Coordination Chemistry of Copper Uptake and Storage for Methane Oxidation

Dennison

2018

Chemistry A European J

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Methanotrophs are remarkable bacteria that utilise large quantities of copper (Cu) to oxidize the potent greenhouse gas methane. To assist in providing the Cu they require for this process some methanotrophs can secrete the Cu‐sequestering modified peptide methanobactin. These small molecules bind CuI with very high affinity and crystal structures have given insight into why this is the case, and also how the metal ion may be released within the cell. A much greater proportion of methanotrophs, genomes of which have been sequenced, possess a member of a newly discovered bacterial family of copper storage proteins (the Csps). These are tetramers of four‐helix bundles whose cores are lined with Cys residues enabling the binding of large numbers of CuI ions. In methanotrophs, a Csp exported from the cytosol stores CuI for the active site of the ubiquitous enzyme that catalyses the oxidation of methane. The presence of cytosolic Csps, not only in methanotrophs but in a wide range of bacteria, challenges the dogma that these organisms have no requirement for Cu in this location. The properties of the Csps, with an emphasis on CuI binding and the structures of the sites formed, are the primary focus of this review.

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Characterization of Methanobactin from Methylosinus sp. LW4

Cited by 35 publications

References 14 publications

Methanobactins: Maintaining copper homeostasis in methanotrophs and beyond

Methanobactins: Maintaining copper homeostasis in methanotrophs and beyond

Insight into Metal Removal from Peptides that Sequester Copper for Methane Oxidation

The Coordination Chemistry of Copper Uptake and Storage for Methane Oxidation

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