Glycyl Radical Enzyme-Associated Microcompartments: Redox-Replete Bacterial Organelles

Ferlez, Bryan; Sutter, Markus; Kerfeld, Cheryl A.

doi:10.1128/mbio.02327-18

Cited by 37 publications

(41 citation statements)

References 76 publications

(157 reference statements)

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“…In addition to the widespread HGT of loci evident from their distribution across phyla (Figure 4), individual shell proteins provide links, such as the BMC‐T dp of EUT3 and SPU6. Likewise, with our observations we can propose steps in the evolution of the encapsulated catalysis; in the canonical PDU1AB and the recently described GRM4 [36, 42], the colors of all shell the same in both loci (Supplementary Data: Locus diagrams). Comparison of the locus diagrams reveals the same gene order, with the PDU signature enzymes interchanged with the GRM4 signature enzyme.…”

Section: Discussionsupporting

confidence: 80%

A Catalog of the Diversity and Ubiquity of Metabolic Organelles in Bacteria

Sutter

Schulz

et al. 2021

Preprint

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Bacterial microcompartments (BMCs) are organelles that segregate segments of metabolic pathways that are incompatible with the surrounding metabolism. These metabolic modules consist entirely of protein, thus they are directly genetically encoded organelles. The BMC membrane is composed of families of proteins that oligomerize into pentagonal and hexagonal building blocks, typically perforated by pores, that tile into a polyhedral shell. The shell protein families are structurally homologous, with the function of the BMC determined by the encapsulated enzymes and the permeability properties of the constituent shell proteins. BMCs can be identified bioinformatically by locating genes encoding shell proteins, which are generally found proximal to those for the encapsulated enzymes. We here performed a large-scale sequence-based analysis of all shell proteins across the bacterial tree of life. With recent advances in genome-resolved metagenomics and the emphasis on “microbial dark matter”, many new genome sequences from diverse and obscure bacterial species clades have become available. We find that locus-specific designations of shell proteins should be supplanted, because higher level patterns of co-occurrence are evident. Moreover, the number of identifiable BMC loci has increased twenty-fold since the last comprehensive census of 2014. While we can assign many to bioinformatically characterized loci, the addition of new types uncovered in this study doubles the number of distinct BMC types described. In addition, we predict several new functional types that expand the range of catalysis encapsulated in BMCs, an intriguing example is an organelle for the degradation of an aromatic substrate, compartmentalized in an unusually simple shell, with potential for bioremediation. Our comprehensive survey of bacterial metabolic organelles underscores that there is compartmentalized dark biochemistry yet to be discovered through genome sequencing. The finding of up to six distinct BMC loci in a single genome underscores the role of BMCs in conferring metabolic flexibility and provides new insights into how certain clades have adapted to or even dominate, as in dysbiosis, an environmental niche. Our catalog provides a rich substrate for downstream experimental characterization of these metabolic modules and broadens the foundation for the development of BMC-based nanoarchitectures for biomedical and bioengineering applications.

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Section: Discussionsupporting

confidence: 80%

A Catalog of the Diversity and Ubiquity of Metabolic Organelles in Bacteria

Sutter

Schulz

et al. 2021

Preprint

Self Cite

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“…Encasing the pathway inside BMCs is essential, since this prevents the toxic acetaldehyde intermediate to damage proteins and RNA/DNA in the cytoplasm [17,37]. The generated reductants are oxidized inside the BMC, while it has been hypothesized that electrons may also be shuttled to the cytosol via specific shell proteins acting as redox carriers [8,17,18,36]. Our metabolite analysis showed enhanced flux via the ATP generating acetate branch in L. monocytogenes, and a reduced flux via the NAD+ regenerating ethanol branch in a 2:1 molar ratio resulting in surplus NADH.…”

Section: Discussionmentioning

confidence: 99%

“…The observed unbalanced production of acetate and ethanol in a 2:1 molar ratio suggests a surplus of NADH, and this requires additional NAD+ regeneration reactions to restore the redox balance. As discussed in previous studies, BMC is a redox-replete compartment which can generate reductants internally or facilitate the transfer of electrons from the cytosol across the shell [8,36]. Recently it has been shown that L. monocytogenes uses a distinctive anaerobic flavin-based EET mechanism to deliver electrons to iron (Fe 3+ ) or to fumarate via membrane-bound fumarate reductase [2].…”

Section: Flavin-based Eet Linked With Bmcs Maintains Redox Balance Ofmentioning

confidence: 99%

Bacterial microcompartments linked to the flavin-based extracellular electron transfer drives anaerobic ethanolamine utilization inListeria monocytogenes

Zeng

Boeren

Bhandula

et al. 2020

Preprint

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Ethanolamine (EA) is a valuable microbial carbon and nitrogen source derived from phospholipids present in cell membranes. EA catabolism is suggested to occur in so-called bacterial microcompartments (BMCs) and activation of EA utilization (eut) genes is linked to bacterial pathogenesis. Despite reports showing that activation of eut in Listeria monocytogenes is regulated by a vitamin B12-binding riboswitch and that upregulation of eut genes occurs in mice, it remains unknown whether EA catabolism is BMC dependent. Here, we provide evidence for BMC-dependent anaerobic EA utilization via metabolic analysis, proteomics and electron microscopy. First, we show B12-induced activation of the eut operon in L. monocytogenes coupled to uptake and utilization of EA thereby enabling growth. Next, we demonstrate BMC formation in conjunction to EA catabolism with the production of acetate and ethanol in a molar ratio of 2:1. Flux via the ATP generating acetate branch causes an apparent redox imbalance due to reduced regeneration of NAD+ in the ethanol branch resulting in a surplus of NADH. We hypothesize that the redox imbalance is compensated by linking eut BMC to anaerobic flavin-based extracellular electron transfer (EET). Using L. monocytogenes wild type, a BMC mutant and a EET mutant, we demonstrate an interaction between BMC and EET and provide evidence for a role of Fe3+ as an electron acceptor. Taken together, our results suggest an important role of anaerobic BMC-dependent EA catabolism in the physiology of L. monocytogenes, with a crucial role for the flavin-based EET system in redox balancing.

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“…Alternatively, their use may suggest O 2 limitation, possibly due to increased heterotrophic biological O 2 demand; pyruvate formate-lyase employs a radical mechanism that generates toxic reactive oxygen species in the presence of oxygen (21). This result was paradoxical, as the biofilm was maintained under light (and, therefore, presumably O 2 ) during the labeling period, but it may reflect either local conditions where rapid heterotroph respiration of organic C fluxes from the cyanobacteria resulted in pockets of hypoxia or internal microcompartments to protect these enzymes from oxygen (22).…”

Section: Nomentioning

confidence: 99%

Nitrogen Source Governs Community Carbon Metabolism in a Model Hypersaline Benthic Phototrophic Biofilm

et al. 2020

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Increasing anthropogenic inputs of fixed nitrogen are leading to greater eutrophication of aquatic environments, but it is unclear how this impacts the flux and fate of carbon in lacustrine and riverine systems. Here, we present evidence that the form of nitrogen governs the partitioning of carbon among members in a genome-sequenced, model phototrophic biofilm of 20 members. Consumption of NO3− as the sole nitrogen source unexpectedly resulted in more rapid transfer of carbon to heterotrophs than when NH4+ was also provided, suggesting alterations in the form of carbon exchanged. The form of nitrogen dramatically impacted net community nitrogen, but not carbon, uptake rates. Furthermore, this alteration in nitrogen form caused very large but focused alterations to community structure, strongly impacting the abundance of only two species within the biofilm and modestly impacting a third member species. Our data suggest that nitrogen metabolism may coordinate coupled carbon-nitrogen biogeochemical cycling in benthic biofilms and, potentially, in phototroph-heterotroph consortia more broadly. It further indicates that the form of nitrogen inputs may significantly impact the contribution of these communities to carbon partitioning across the terrestrial-aquatic interface. IMPORTANCE Anthropogenic inputs of nitrogen into aquatic ecosystems, and especially those of agricultural origin, involve a mix of chemical species. Although it is well-known in general that nitrogen eutrophication markedly influences the metabolism of aquatic phototrophic communities, relatively little is known regarding whether the specific chemical form of nitrogen inputs matter. Our data suggest that the nitrogen form alters the rate of nitrogen uptake significantly, whereas corresponding alterations in carbon uptake were minor. However, differences imposed by uptake of divergent nitrogen forms may result in alterations among phototroph-heterotroph interactions that rewire community metabolism. Furthermore, our data hint that availability of other nutrients (i.e., iron) might mediate the linkage between carbon and nitrogen cycling in these communities. Taken together, our data suggest that different nitrogen forms should be examined for divergent impacts on phototrophic communities in fluvial systems and that these anthropogenic nitrogen inputs may significantly differ in their ultimate biogeochemical impacts.

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Glycyl Radical Enzyme-Associated Microcompartments: Redox-Replete Bacterial Organelles

Cited by 37 publications

References 76 publications

A Catalog of the Diversity and Ubiquity of Metabolic Organelles in Bacteria

A Catalog of the Diversity and Ubiquity of Metabolic Organelles in Bacteria

Bacterial microcompartments linked to the flavin-based extracellular electron transfer drives anaerobic ethanolamine utilization inListeria monocytogenes

Nitrogen Source Governs Community Carbon Metabolism in a Model Hypersaline Benthic Phototrophic Biofilm

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