<i>Salmonella enterica</i> synthesizes 5,6‐dimethylbenzimidazolyl‐(DMB)‐α‐riboside. Why some Firmicutes do not require the canonical DMB activation system to synthesize adenosylcobalamin

Mattes, Theodoric A.; Escalante‐Semerena, Jorge C.

doi:10.1111/mmi.13555

Cited by 15 publications

(26 citation statements)

References 41 publications

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“…2a, α-ribazole salvaging); we found CblS in 363 species (3.2%), mostly in the Firmicutes phylum (Fig. 5a, b, inner rings) [42, 52]. A higher proportion of bacteria, 1041 species (9.1%), have a CbiZ annotation (Fig.…”

Section: Resultsmentioning

confidence: 95%

Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics

et al. 2018

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The vitamin B 12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria.

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Section: Resultsmentioning

confidence: 95%

Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics

et al. 2018

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“…For example, Salmonella enterica produces corrinoids de novo under anaerobic conditions and can produce both pseudocobalamin and, if supplemented with DMB, also cobalamin (Anderson et al , ). Three cobamide‐dependent enzymes (methionine synthase MetH, ethanolamine ammonia‐lyase EutBC and propanediol dehydratase PduCDE) can utilize both cobalamin and pseudocobalamin to support growth of S. enterica (Anderson et al , ; Mattes and Escalante‐Semerena, ). Additionally, MetH function was supported when supplemented with p ‐cresolylcobamide, but not EutBC or PduCDE (Chan and Escalante‐Semerena, ).…”

Section: Introductionmentioning

confidence: 99%

Specificity of cobamide remodeling, uptake and utilization in Vibrio cholerae

Tyrell

Beld

2019

Molecular Microbiology

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Cobamides are a group of compounds including vitamin B 12 that can vary at the lower base position of the nucleotide loop. They are synthesized de novo by only a subset of prokaryotes, but some organisms encode partial biosynthesis pathways for converting one variant to another (remodeling) or completing biosynthesis from an intermediate (corrinoid salvaging). Here, we explore the cobamide specificity in Vibrio cholerae through examination of three natural variants representing major cobamide groups: commercially available cobalamin, and isolated pseudocobalamin and p-cresolylcobamide. We show that BtuB, the outer membrane corrinoid transporter, mediates the uptake of all three variants and the intermediate cobinamide. Our previous work suggested that V. cholerae could convert pseudocobalamin produced by cyanobacteria into cobalamin. In this work, cobamide specificity in V. cholerae is demonstrated by remodeling of pseudocobalamin and salvaging of cobinamide to produce cobalamin. Cobamide remodeling in V. cholerae is distinct from the canonical pathway requiring amidohydrolase CbiZ, and heterologous expression of V. cholerae CobS was sufficient for remodeling. Furthermore, function of V. cholerae cobamide-dependent methionine synthase MetH was robustly supported by cobalamin and p-cresolylcobamide, but not pseudocobalamin. Notably, the inability of V. cholerae to produce and utilize pseudocobalamin contrasts with enteric bacteria like Salmonella.

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“…7A, Route 1). Alternately, the dephosphorylation can occur nonenzymatically (54). Further, the enzyme cobalamin synthase encoded by the gene cobS, which is responsible for attaching the activated lower ligand to a cobinamide backbone, has been reported to use both DMB-RP 7 and DMB-R 20 as substrates (55) (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…7B), and further characterization of these and other CobS and CobC homologs from obligate anaerobes harboring a bza operon will be required to validate these findings. Additionally, DMB-R 20 is shown to occur in cobamideproducing organisms-it has been shown to be utilized by certain microorganisms such as Listeria innocua and Geobacillus kaustophilus and fluxed into the cobalamin biosynthesis pathway (54,57).…”

Section: Discussionmentioning

confidence: 99%

CobT and BzaC catalyze the regiospecific activation and methylation of the 5-hydroxybenzimidazole lower ligand in anaerobic cobamide biosynthesis

Mathur

Sreyas

Datar

et al. 2020

Journal of Biological Chemistry

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Vitamin B12 and other cobamides are essential cofactors required by many organisms and are synthesized by a subset of prokaryotes via distinct aerobic and anaerobic routes. The anaerobic biosynthesis of 5,6-dimethylbenzimidazole (DMB), the lower ligand of vitamin B12, involves five reactions catalyzed by the bza operon gene products, namely, the hydroxybenzimidazole synthase BzaAB/ BzaF, phosphoribosyltransferase CobT, and three methyltransferases, BzaC, BzaD, and BzaE, that conduct three distinct methylation steps. Of these, the methyltransferases that contribute to benzimidazole lower ligand diversity in cobamides remain to be characterized, and the precise role of the bza operon protein CobT is unclear. In this study, we used the bza operon (comprising bzaA-bzaB-cobT-bzaC) from the anaerobic bacterium Moorella thermoacetica to examine the role of CobT and investigate the activity of the first methyltransferase BzaC. We studied the phosphoribosylation catalyzed by MtCobT and found that it regiospecifically activates 5-hydroxybenzimidazole (5-OHBza) to form the 5-OHBza-ribotide (5-OHBza-RP) isomer as the sole product. Next, we characterized the domains of MtBzaC and reconstituted its methyltransferase activity with the predicted substrate 5-OHBza and with two alternative substrates, the MtCobT product 5-OHBza-RP and its riboside derivative 5-OHBza-R. Unexpectedly, we found that 5-OHBza-R is the most favored MtBzaC substrate. Our results collectively explain the long-standing observation that the attachment of the lower ligand in anaerobic cobamide biosynthesis is regiospecific. In conclusion, we validate MtBzaC as a SAM:hydroxybenzimidazole-riboside methyltransferase (HBIR-OMT). Finally, we propose a new pathway for the synthesis and activation of the benzimidazolyl lower ligand in anaerobic cobamide biosynthesis.

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Salmonella enterica synthesizes 5,6‐dimethylbenzimidazolyl‐(DMB)‐α‐riboside. Why some Firmicutes do not require the canonical DMB activation system to synthesize adenosylcobalamin

Cited by 15 publications

References 41 publications

Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics

Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics

Specificity of cobamide remodeling, uptake and utilization in Vibrio cholerae

CobT and BzaC catalyze the regiospecific activation and methylation of the 5-hydroxybenzimidazole lower ligand in anaerobic cobamide biosynthesis

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