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Revision as of 23:38, 28 October 2017
VITAMIN B12 METABOLICS
“Vitamin B12 deficiency is a common but serious condition...a deficiency may lead to disruption of DNA and cell metabolism and thus have serious clinical consequences.”
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].
- Vitamin B12 is composed of a corrin ring, centralized cobalt, and covalently bound upper and lower axial ligands.
- For vitamin B12 to be active in mammals, the lower ligand must be constructed with 5,6-dimethylbenzimidazole and α-ribosole-5-phosphate.
- 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.
- 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.
- Without the glycoprotein intrinsic factor, vitamin B12 cannot be absorbed.
- The genes ssuE and bluB are absent in PCC 7942.
- In order to induce the synthesis of active B12 in PCC 7942, these previously absent genes must be artificially integrated into the organism’s genome.
- These gene inserts will allow 5,6-DMB to be synthesized in the host.
- PCC 7942 has the necessary genes (cobU, pgam3, cobS) to complete the synthesis of vitamin B12 with 5,6-DMB as the lower ligand.
- The result is synthesis of active vitamin B12 within PCC 7942.