Most cyanobacteria, including PCC 7942 and A. platensis, produce pseudo vitamin B₁₂, which is a form of vitamin B₁₂ that is inactive in mammals^{[10, 11]}. Active B₁₂ is important for nucleotide synthesis and the human metabolism of branched amino acids and odd-chain fatty acids. It acts as a cofactor in synthesis of methionine and succinyl-CoA^[12]. Methionine is an essential amino acid; its upregulation increases biological value by cellular protein composition^[13]. Increased vitamin B₁₂ levels upregulates methionine synthesis, causing an increase in biological value. An increase in methionine levels additionally boosts vitamin B₉ (folate) availability^[14].

Active vitamin B₁₂ proves to be a leading global vitamin deficiency and one of the most difficult vitamins to naturally consume, especially for vegetarians^[15]. Vitamin B₁₂ deficiency can lead to megaloblastic anemia and demyelinating nervous system disease^[16]. Additionally, both vitamins B₁₂ and B₉ are considered important prenatal vitamins for nervous system development^[17].

What makes Vitamin B₁₂ active?

1. Vitamin B₁₂ is composed of a corrin ring, centralized cobalt, and covalently bound upper and lower axial ligands.


2. For vitamin B₁₂ to be active in mammals, the lower ligand must be constructed with 5,6-dimethylbenzimidazole and α-ribosole-5-phosphate.


3. Without these two compounds, the cell cannot synthesize the 5,6-dimethylbenzimidazolyl nucleotide moiety (5,6-DMB) de novo and instead uses cellular adenine as the lower ligand, creating pseudo-B₁₂.


4. 5,6-DMB, as a lower ligand, binds the glycoprotein intrinsic factor to cobalamin, which aids in transport of the B₁₂ molecule within the mammalian gastrointestinal tract.


5. Without the glycoprotein intrinsic factor, vitamin B₁₂ cannot be absorbed.

Project Homepage

---

The Project

Click here to learn more!

---

Acetaminophen

Modeling

Results

Target Organism

Parts

---

[10] K. E. Helliwell, A. D. Lawrence, A. Holzer, U. J. Kudahl, S. Sasso, B. Kr ̈autler, D. J. Scanlan, M. J. Warren, and A. G. Smith, “Cyanobacteria and Eukaryotic Algae Use Different Chemical Variants of Vitamin B12,” Current biology: CB, vol. 26, pp. 999–1008, Apr. 2016.

[11] V. Karuppiah, W. Sun, and Z. Li, “Natural Products of Actinobacteria Derived from Marine Organisms,” in Studies in Natural Products Chemistry, vol. 48, pp. 417-446, Elsevier, 2016. DOI: 10.1016/B978-0-444-63602-7.00013-8.

[12] P. Deptula, P. Kylli, B. Chamlagain, L. Holm, R. Kostiainen, V. Piironen, K. Savijoki, and P. Varmanen, “BluB/CobT2 fusion enzyme activity reveals mechanisms responsible for production of active form of vitamin B₁₂ by Propionibacterium freudenreichii,” Microbial Cell Factories, vol. 14, p. 186, Nov. 2015.

[13] D. L. R. Narasimha, G. S. Venkataraman, S. K. Duggal, and B. O. Eggum, “Nutritional quality of the blue-green alga Spirulina platensis geitler,” Journal of the Science of Food and Agriculture, vol. 33, pp. 456{460, May 1982.

[14] M. Fenech, “Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity,” Mutation Research, vol. 733, pp. 21-33, May 2012.

[15] B. Hemmer, F. X. Glocker, M. Schumacher, G. Deuschl, and C. H. Lucking, “Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings,” Journal of Neurology, Neurosurgery, and Psychiatry, vol. 65, pp. 822-827, Dec. 1998.

[16] S. P. Stabler, “Vitamin B12 Deficiency,” New England Journal of Medicine, vol. 368, pp. 149-160, Jan. 2013.

[17] M. T. Steen, A. M. Boddie, A. J. Fisher, W. Macmahon, D. Saxe, K. M. Sullivan, P. P. Dembure, and L. J. Elsas, “Neural-tube defects are associated with low concentrations of cobalamin (vitamin B12) in amniotic fluid,” Prenatal Diagnosis, vol. 18, pp. 545-555, June 1998.