Methanobactin rapidly facilitates biliary copper excretion in a Wilson disease rat model visualised by Cu PET/MRI.

Background And Purpose: Methanobactins are peptides with high copper affinity and potential to treat Wilson disease. We examined how two methanobactins (ARBM101 and MB-OB3b) affected copper handling in the LPP Atp7b Wilson disease rat model, compared to penicillamine or saline, by Cu positron emission tomography/magnetic resonance imaging. Heterozygotes served as controls.

Heterologous Biosynthesis of Methanobactin from sp. Strain SB2 in OB3b.

Aerobic methanotrophs, or methane-consuming microbes, are strongly dependent on copper for their activity. To satisfy this requirement, some methanotrophs produce a copper-binding compound, or chalkophore, called methanobactin (MB). In addition to playing a critical role in methanotrophy, MB has also been shown to have great promise in treating copper-related human diseases, perhaps most significantly Wilson's disease.

Copper impairs the intestinal barrier integrity in Wilson disease.

In Wilson disease (WD), liver copper (Cu) excess, caused by mutations in the ATPase Cu transporting beta (ATP7B), has been extensively studied. In contrast, in the gastrointestinal tract, responsible for dietary Cu uptake, ATP7B malfunction is poorly explored. We therefore investigated gut biopsies from WD patients and compared intestines from two rodent WD models and from human ATP7B knock-out intestinal cells to their respective wild-type controls.

MmoD regulates soluble methane monooxygenase and methanobactin production in OB3b.

Aerobic methanotrophs play a critical role in the global carbon cycle, particularly in controlling net emissions of methane to the atmosphere. As methane is a much more potent greenhouse gas than carbon dioxide, there is increasing interest in utilizing these microbes to mitigate future climate change by increasing their ability to consume methane. Any such efforts, however, require a detailed understanding of how to manipulate methanotrophic activity.

Improved scientific knowledge of methanogenesis and methanotrophy needed to slow climate change during the next 30 years.

Owing to the high radiative forcing and short atmospheric residence time of methane, abatement of methane emissions offers a crucial opportunity for effective, rapid slowing of climate change. Here, we report on a colloquium jointly sponsored by the American Society for Microbiology and the American Geophysical Union, where 35 national and international experts from academia, the private sector, and government met to review understanding of the microbial processes of methanogenesis and methanotrophy. The colloquium addressed how advanced knowledge of the microbiology of methane production and consumption could inform waste management, including landfills and composts, and three areas of agricultural management: enteric emissions from ruminant livestock, manure management, and rice cultivation.

Inhibition of nitrous oxide reduction in forest soil microcosms by different forms of methanobactin.

Copper plays a critical role in controlling greenhouse gas emissions as it is a key component of the particulate methane monooxygenase and nitrous oxide reductase. Some methanotrophs excrete methanobactin (MB) that has an extremely high copper affinity. As a result, MB may limit the ability of other microbes to gather copper, thereby decreasing their activity as well as impacting microbial community composition.

Adsorption and intracellular uptake of mercuric mercury and methylmercury by methanotrophs and methylating bacteria.

The cell surface adsorption and intracellular uptake of mercuric mercury Hg(II) and methylmercury (MeHg) are important in determining the fate and transformation of Hg in the environment. However, current information is limited about their interactions with two important groups of microorganisms, i.e.

Crystal structure of MbnF: an NADPH-dependent flavin monooxygenase from Methylocystis strain SB2.

Methanobactins (MBs) are ribosomally produced and post-translationally modified peptides (RiPPs) that are used by methanotrophs for copper acquisition. The signature post-translational modification of MBs is the formation of two heterocyclic groups, either an oxazolone, pyrazinedione or imidazolone group, with an associated thioamide from an X-Cys dipeptide. The precursor peptide (MbnA) for MB formation is found in a gene cluster of MB-associated genes.

Multiple Mechanisms for Copper Uptake by Methylosinus trichosporium OB3b in the Presence of Heterologous Methanobactin.

Methanotrophs require copper for their activity as it plays a critical role in the oxidation of methane to methanol. To sequester copper, some methanotrophs secrete a copper-binding compound termed methanobactin (MB). MB, after binding copper, is reinternalized via a specific outer membrane TonB-dependent transporter (TBDT).

Diffusion of H S from anaerobic thiolated ligand biodegradation rapidly generates bioavailable mercury.

Methylmercury is a potent neurotoxin that biomagnifies through food webs and which production depends on anaerobic microbial uptake of inorganic mercury (Hg) species. One outstanding knowledge gap in understanding Hg methylation is the nature of bioavailable Hg species. It has become increasingly obvious that Hg bioavailability is spatially diverse and temporally dynamic but current models are mostly built on single thiolated ligand systems, omitting ligand exchanges and interactions, or the inclusion of dissolved gaseous phases.

Updated Genome Sequence of the Facultative Methanotroph sp. Strain SB2.

The genome of sp. strain SB2, which was previously isolated from a spring bog in southeast Michigan, was sequenced using long-read sequencing technology. This new sequencing and assembly effort yielded a complete assembly of the genome in a single contig.

Variable Inhibition of Nitrous Oxide Reduction in Denitrifying Bacteria by Different Forms of Methanobactin.

Aerobic methanotrophic activity is highly dependent on copper availability, and methanotrophs have developed multiple strategies to collect copper. Specifically, when copper is limiting (ambient concentrations less than 1 μM), some methanotrophs produce and secret a small modified peptide (less than 1,300 Da) termed methanobactin (MB) that binds copper with high affinity. As MB is secreted into the environment, other microbes that require copper for their metabolism may be inhibited as MB may make copper unavailable; e.

MbnC Is Not Required for the Formation of the N-Terminal Oxazolone in the Methanobactin from Methylosinus trichosporium OB3b.

Methanobactins (MBs) are ribosomally synthesized and posttranslationally modified peptides (RiPPs) produced by methanotrophs for copper uptake. The posttranslational modification that defines MBs is the formation of two heterocyclic groups with associated thioamines from X-Cys dipeptide sequences. Both heterocyclic groups in the MB from Methylosinus trichosporium OB3b (MB-OB3b) are oxazolone groups.

Two TonB-Dependent Transporters in Methylosinus trichosporium OB3b Are Responsible for Uptake of Different Forms of Methanobactin and Are Involved in the Canonical "Copper Switch".

Copper is an important component of methanotrophic physiology, as it controls the expression and activity of alternative forms of methane monooxygenase (MMO). To collect copper, some methanotrophs secrete a chalkophore- or copper-binding compound called methanobactin (MB). MB is a ribosomally synthesized posttranslationally modified polypeptide (RiPP) that, after binding copper, is collected by MbnT, a TonB-dependent transporter (TBDT).

Evidence for methanobactin "Theft" and novel chalkophore production in methanotrophs: impact on methanotrophic-mediated methylmercury degradation.

Aerobic methanotrophy is strongly controlled by copper, and methanotrophs are known to use different mechanisms for copper uptake. Some methanotrophs secrete a modified polypeptide-methanobactin-while others utilize a surface-bound protein (MopE) and a secreted form of it (MopE*) for copper collection. As different methanotrophs have different means of sequestering copper, competition for copper significantly impacts methanotrophic activity.

Spectroscopic and computational investigations of organometallic complexation of group 12 transition metals by methanobactins from Methylocystis sp. SB2.

Methanotrophic bacteria catalyze the aerobic oxidation of methane to methanol using Cu-containing enzymes, thereby exerting a modulating influence on the global methane cycle. To facilitate the acquisition of Cu ions, some methanotrophic bacteria secrete small modified peptides known as "methanobactins," which strongly bind Cu and function as an extracellular Cu recruitment relay, analogous to siderophores and Fe. In addition to Cu, methanobactins form complexes with other late transition metals, including the Group 12 transition metals Zn, Cd, and Hg, although the interplay among solution-phase configurations, metal interactions, and the spectroscopic signatures of methanobactin-metal complexes remains ambiguous.

Complete Genome Sequences of Two Gammaproteobacterial Methanotrophs Isolated from a Mercury-Contaminated Stream.

The genomes of sp. strain EFPC1 and sp. strain EFPC2, isolated from a mercury-contaminated stream in Oak Ridge, Tennessee, were sequenced.

Oxygen Generation via Water Splitting by a Novel Biogenic Metal Ion-Binding Compound.

Methanobactins (MBs) are small (<1,300-Da) posttranslationally modified copper-binding peptides and represent the extracellular component of a copper acquisition system in some methanotrophs. Interestingly, MBs can bind a range of metal ions, with some being reduced after binding, e.g.

Enhancement of Nitrous Oxide Emissions in Soil Microbial Consortia via Copper Competition between Proteobacterial Methanotrophs and Denitrifiers.

Unique means of copper scavenging have been identified in proteobacterial methanotrophs, particularly the use of methanobactin, a novel ribosomally synthesized, post-translationally modified polypeptide that binds copper with very high affinity. The possibility that copper sequestration strategies of methanotrophs may interfere with copper uptake of denitrifiers and thereby enhance NO emissions was examined using a suite of laboratory experiments performed with rice paddy microbial consortia. Addition of purified methanobactin from Methylosinus trichosporium OB3b to denitrifying rice paddy soil microbial consortia resulted in substantially increased NO production, with more pronounced responses observed for soils with lower copper content.

Synergistic Effects of a Chalkophore, Methanobactin, on Microbial Methylation of Mercury.

Microbial production of the neurotoxin methylmercury (MeHg) is a significant health and environmental concern, as it can bioaccumulate and biomagnify in the food web. A chalkophore or a copper-binding compound, termed methanobactin (MB), has been shown to form strong complexes with mercury [as Hg(II)] and also enables some methanotrophs to degrade MeHg. It is unknown, however, if Hg(II) binding with MB can also impede Hg(II) methylation by other microbes.

Methanobactin from methanotrophs: genetics, structure, function and potential applications.

Aerobic methane-oxidizing bacteria of the Alphaproteobacteria have been found to express a novel ribosomally synthesized post-translationally modified polypeptide (RiPP) termed methanobactin (MB). The primary function of MB in these microbes appears to be for copper uptake, but MB has been shown to have multiple capabilities, including oxidase, superoxide dismutase and hydrogen peroxide reductase activities, the ability to detoxify mercury species, as well as acting as an antimicrobial agent. Herein, we describe the diversity of known MBs as well as the genetics underlying MB biosynthesis.

Methanotrophy - Environmental, Industrial and Medical Applications.

Aerobic methanotrophs are an intriguing group of microbes with the singular ability to consume methane as their sole source of carbon and energy. As such, methanotrophs are receiving increased attention to control methane emissions to limit future climate change. Methanotrophs have a wide range of other applications, including pollutant remediation and methane valorization (e.

The origin of aerobic methanotrophy within the Proteobacteria.

Aerobic methanotrophs play critical roles in the global carbon cycle, but despite their environmental ubiquity, they are phylogenetically restricted. Via bioinformatic analyses, it is shown that methanotrophy likely arose from methylotrophy from the lateral gene transfer of either of the two known forms of methane monooxygenase (particulate and soluble methane monooxygenases). Moreover, it appears that both known forms of pyrroloquinoline quinone-dependent methanol dehydrogenase (MeDH) found in methanotrophs-the calcium-containing Mxa-MeDH and the rare earth element-containing Xox-MeDH-were likely encoded in the genomes before the acquisition of the methane monooxygenases (MMOs), but that some methanotrophs subsequently received an additional copy of Xox-MeDH-encoding genes via lateral gene transfer.

Methanobactin from Methylosinus trichosporium OB3b inhibits NO reduction in denitrifiers.

Methanotrophs synthesize methanobactin, a secondary metabolite that binds copper with an unprecedentedly high affinity. Such a strategy may provide methanotrophs a "copper monopoly" that can inhibit the activity of copper-containing enzymes of other microbes, e.g.