Anaerobic biosynthesis of the lower ligand of vitamin B 12
Open accessAbstract
Significance: Vitamin B 12 is required by humans and a variety of other organisms for diverse metabolic processes, but is produced only by a subset of microorganisms. The anaerobic biosynthesis of the “lower ligand” of B 12 , 5,6-dimethylbenzimidazole (DMB), is the only unknown component of the B 12 biosynthetic pathway. We report the identification of the bzaABCDE genes that are necessary and sufficient for the anaerobic biosynthesis of DMB. We have characterized the role of each of the bza genes and identified three intermediates in the pathway. This finding not only completes the B 12 biosynthesis pathway but also enables the sequence-based prediction of cobamides synthesized by anaerobic microorganisms.
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The anaerobic synthesis of DMB is performed by the bzaABCDE gene products, starting from AIR.
“The anaerobic synthesis of the cobalamin lower ligand dimethylbenzimidazole (DMB) is performed by the bzaABCDE gene products [39], starting from 5‐aminoimidazole ribotide (AIR), an intermediate of thiamine and purine biosynthesis.”
From Evidence for corrin biosynthesis in the last universal common ancestor (2025) · cites this paper as [39]
In some organisms, only bzaF is present, generating HBI as the cobamide lower ligand.
“In some organisms, only the product of bzaF, a radical SAM enzyme homologous to bzaA, bzaB and thiC products, is present [39, 109], generating 5‐hydroxybenzimidazole (HBI) as the cobamide lower ligand (Fig. 1C).”
From Evidence for corrin biosynthesis in the last universal common ancestor (2025) · cites this paper as [39]
Among enzymes involved in synthesis of cobalamin lower ligand, only BzaF is well conserved across the bacterial-archaeal divide.
“Among the enzymes involved in the synthesis of the cobalamin lower ligand, only BzaF, which catalyzes the synthesis of 5‐hydroxybenzimidazole (HBI) [39], is well conserved across the bacterial–archaeal divide”
From Evidence for corrin biosynthesis in the last universal common ancestor (2025) · cites this paper as [39]
Cites
Construction of Escherichia coli K‐12 in‐frame, single‐gene knockout mutants: the Keio collection
Baba, T., Ara, T., Hasegawa, M., Takai, Y., Okumura, Y., Baba, M., Datsenko, K. A., Tomita, M., Wanner, B. L., & Mori, H. (2006) · Molecular Systems Biology · doi:10.1038/msb4100050 · Cited by 7,858 · see citing works
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Cyanobacteria and eukaryotic algae use different chemical variants of vitamin B12
Helliwell, K. E., Lawrence, A. D., Holzer, A., Kudahl, U. J., Sasso, S., Kräutler, B., Scanlan, D. J., Warren, M. J., & Smith, A. G. (2016) · Current Biology · doi:10.1016/j.cub.2016.02.041 · Cited by 250 · see citing works
On the evolution of coenzyme biosynthesis
Kirschning, A. (2022) · Natural Product Reports · doi:10.1039/d2np00037g · Cited by 37 · see citing works
Evidence for corrin biosynthesis in the last universal common ancestor
Modjewski, L. D., Karavaeva, V., Mrnjavac, N., Knopp, M., Martin, W. F., & Sousa, F. L. (2025) · The FEBS Journal · doi:10.1111/febs.17367 · Cited by 15 · see citing works
“In some organisms, only the product of bzaF , a radical SAM enzyme homologous to bzaA , bzaB and thiC products, is pre-sent [39,109], generating 5-hydroxybenzimidazole (HBI) as the cobamide lower ligand (Fig.”
Influential
- Authors
- Hazra, A. B., Han, A. W., Mehta, A. P., Mok, K. C., Osadchiy, V., Begley, T. P., & Taga, M. E.
- Affiliations
- University of California, Berkeley (US)
- Texas A&M University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-08-05
- Volume
- 112
- Issue
- 34
- Pages
- 10792-10797
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4553811
- OpenAlex
- W1828900086
- Cited by
- 116
- References
- 1
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 12 · 2023: 21 · 2022: 15 · 2021: 6 · 2020: 12 · 2019: 8 · 2018: 14 · 2017: 9 · 2016: 5 · 2015: 3
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OakTrust (Texas A&M University Libraries) (submittedVersion)
- Funders
- National Science Foundation (MCB1122046)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Keywords
- vitamin B12 biosynthesis, vitamin B12, 5,6-dimethylbenzimidazole, Eubacterium limosum
- MeSH terms
- Anaerobiosis, Archaea, Bacterial Proteins, Benzimidazoles, DNA, Recombinant, Escherichia coli, Eubacterium, Genes, Bacterial, Molecular Sequence Data, Phylogeny, Recombinant Proteins, Salmonella typhimurium, Sequence Homology, Nucleic Acid, Vitamin B 12, Molecular Structure, Sequence Alignment, Genes, Archaeal, Geobacter, Corrinoids, Metabolic Networks and Pathways, Moorella, Riboswitch
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