Twenty Years of Radical SAM! The Genesis of the Superfamily

Booker, Squire J.; Lloyd, Cody T

doi:10.1021/acsbiomedchemau.2c00078

Cited by 22 publications

(7 citation statements)

References 69 publications

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“…Nevertheless, experimental evidence provided in this study shows the involvement of YtqA in the biosynthesis of nmn 5 s 2 U; therefore, we propose renaming this enzyme as MnmL (Figure 8). Our current model is that MnmL-MnmM can promote the conversion of cmnm 5 s 2 U into mnm 5 s 2 U. MnmL (YtqA) is classified as a member of radical SAM enzymes, which are known to catalyze a range of diverse chemical transformations triggered by the generation of a 5’-deoxyadenosyl radical (dAdo ● ) from SAM (38). This dAdo ● could abstract an H-atom from cmnm 5 s 2 U, causing oxidative decarboxylation by forming an xnm 5 s 2 U intermediate that could further react to yield mnm 5 s 2 U.…”

Section: Discussionmentioning

confidence: 99%

Alternate routes to mnm⁵s²U synthesis in Gram-positive bacteria

Jaroch,

Sun,

Tsui

et al. 2023

Preprint

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The wobble bases of tRNAs that decode split codons are often heavily modified. In Bacteria tRNAGlu,Gln,Aspcontain a variety of xnm5s2U derivatives. The synthesis pathway for these modifications is complex and fully elucidated only in a handful of organisms, including the Gram-negativeEscherichia coliK12 model. Despite the ubiquitous presence of mnm5s2U modification, genomic analysis shows the absence ofmnmCorthologous genes, suggesting the occurrence of alternate biosynthetic schemes for the installation of this modification. Using a combination of comparative genomics and genetic studies, a member of the YtqA subgroup of the Radical Sam superfamily was found to be involved in the synthesis of mnm5s2U in bothBacillus subtilisandStreptococcus mutans. This protein, renamed MnmL, is encoded in an operon with the recently discovered MnmM methylase involved in the methylation of the pathway intermediate nm5s2U into mnm5s2U inB. subtilis. Analysis of tRNA modifications of bothS. mutansandStreptococcus pneumoniaeshows that growth conditions and genetic backgrounds influence the ratios of pathways intermediates in regulatory loops that are not yet understood. The MnmLM pathway is widespread along the bacterial tree, with some phyla, such as Bacilli, relying exclusively on these two enzymes. The occurrence of fusion proteins, alternate arrangements of biosynthetic components, and loss of biosynthetic branches provide examples of biosynthetic diversity to retain a conserved tRNA modification in nature.ImportanceThe xnm5s2U modifications found in several tRNAs at the wobble base position are widespread in Bacteria where they have an important role in decoding efficiency and accuracy. This work identifies a novel enzyme (MnmL) that is a member of a subgroup of the very versatile Radical SAM superfamily and is involved in the synthesis of mnm5s2U in several Gram-positive bacteria, including human pathogens. This is another novel example of a non-orthologous displacement in the field of tRNA modification synthesis, showing how different solutions evolve to retain U34 tRNA modifications.

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Section: Discussionmentioning

confidence: 99%

Alternate routes to mnm⁵s²U synthesis in Gram-positive bacteria

Jaroch,

Sun,

Tsui

et al. 2023

Preprint

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“…In addition to providing added metabolic functionality, there is also evidence that viruses in the brine pool could be conferring helpful genes for stress tolerance. The high expression of genes such as GTP cyclohydrolase, QueC, and the Radical SAM superfamily gene at the pool zone suggests that these could be helping with anoxic and hypersaline stress (72)(73)(74).…”

Section: Active Viral Ecology At the Brine Poolmentioning

confidence: 99%

Active prokaryotic and eukaryotic viral ecology across spatial scale in a deep-sea brine pool

Minch,

Chakraborty,

Purkis

et al. 2024

Preprint

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Deep-sea brine pools represent rare, extreme environments that focus biodiversity at bathyal to abyssal depths. Despite their small size and distribution, brine pools represent important ecosystems to study because they provide unique insight into the limits of life on Earth, and by analogy, the plausibility of life beyond it. A distinguishing feature of many brine pools is the presence of thick benthic microbial mats which develop at the brine-seawater interface. While these bacterial and archaeal communities have received moderate attention, little is known about the viral communities and their interactions with host populations in these environments. To bridge this knowledge gap, we leveraged metagenomic and metatranscriptomic data from three distinct zones within the NEOM brine pool system (Gulf of Aqaba) to gain insights into the active viral ecology around the pools. Here, we report a remarkable diversity and activity of viruses of all nucleic acid types and genome sizes that infect prokaryotic and eukaryotic hosts in this environment. These include giant viruses (phylum: Nucleocytoviricota), RNA viruses, jumbo phages, and polinton-like viruses (PLVs). Many of these appeared to form distinct clades showing the possibility of untapped viral diversity in the brine pool ecosystem. Zone-specific differences in viral community composition and infection strategy were also observed with lysogenic phages seeming to dominate the bacterial mat further away from the pools center. Through host matching, viruses infecting metabolically important bacteria and archaea were observed - including a linkage between a jumbo phage and a key manganese-oxidizing and arsenic-metabolizing bacterium. Our findings shed light on the role of viruses in modulating the brine pool microbial community dynamics and biogeochemistry through revealing novel viral diversity, host-virus associations, and spatial-scale heterogeneity in viral dynamics in these extreme environments. These results will provide crucial foundation for further investigation into the adaptations of viruses and their microbial hosts in extreme habitats in the marine ecosystem.

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“…Virtually every cell on Earth ingeniously harnesses FeS clusters as crucial cofactors in a multitude of biological processes [1,2]. FeS enzymes are integral to mitochondrial respiration [3], the TCA cycle [4], nitrogen fixation [5], DNA replication and repair [6][7][8][9], protein translation [10], heme and cofactor biosynthesis [11][12][13], and sensing and regulation of iron levels [4,14,15], among others. FeS clusters play both structural and functional roles by acting in electron transfer processes, oxidoreductive reactions, and protein conformational changes-an ability not inherently shared by other metal ions [2,16,17].…”

Section: Iron-sulfur Clusters As Essential Cofactors In Cells From Ba...mentioning

confidence: 99%

Tip of the Iceberg: A New Wave of Iron–Sulfur Cluster Proteins Found in Viruses

Heffner,

Maio

2024

Inorganics

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Viruses rely on host cells to replicate their genomes and assemble new viral particles. Thus, they have evolved intricate mechanisms to exploit host factors. Host cells, in turn, have developed strategies to inhibit viruses, resulting in a nuanced interplay of co-evolution between virus and host. This dynamic often involves competition for resources crucial for both host cell survival and virus replication. Iron and iron-containing cofactors, including iron–sulfur clusters, are known to be a heavily fought for resource during bacterial infections, where control over iron can tug the war in favor of the pathogen or the host. It is logical to assume that viruses also engage in this competition. Surprisingly, our knowledge about how viruses utilize iron (Fe) and iron–sulfur (FeS) clusters remains limited. The handful of reviews on this topic primarily emphasize the significance of iron in supporting the host immune response against viral infections. The aim of this review, however, is to organize our current understanding of how viral proteins utilize FeS clusters, to give perspectives on what questions to ask next and to propose important avenues for future investigations.

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Twenty Years of Radical SAM! The Genesis of the Superfamily

Cited by 22 publications

References 69 publications

Alternate routes to mnm⁵s²U synthesis in Gram-positive bacteria

Alternate routes to mnm⁵s²U synthesis in Gram-positive bacteria

Active prokaryotic and eukaryotic viral ecology across spatial scale in a deep-sea brine pool

Tip of the Iceberg: A New Wave of Iron–Sulfur Cluster Proteins Found in Viruses

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Twenty Years of Radical SAM! The Genesis of the Superfamily

Cited by 22 publications

References 69 publications

Alternate routes to mnm5s2U synthesis in Gram-positive bacteria

Alternate routes to mnm5s2U synthesis in Gram-positive bacteria

Active prokaryotic and eukaryotic viral ecology across spatial scale in a deep-sea brine pool

Tip of the Iceberg: A New Wave of Iron–Sulfur Cluster Proteins Found in Viruses

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Product

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Alternate routes to mnm⁵s²U synthesis in Gram-positive bacteria

Alternate routes to mnm⁵s²U synthesis in Gram-positive bacteria