Vitamin B12,biosynthesis

In the context of a chemical study related to problems of vitamin B12 biosynthesis, peripheral C-methylation of the magnesium complex of tctct-OEPc (17) was reported to yield a mixture of isomeric products (18a-c) (83AG(E)631). A similar reaction was found to occur at C-12 of nonamethyl pyrrocorphin (19). One of the by-products of this reaction is the seco-corphinoid derivative 20, which, on complexation with Ni(II) acetate, cyclizes to give an Ni(II) corrinate (21) (84CC583). 

Progress in the synthesis of chlorophylls and bacteriochlorophylls (di- and tetra-hydro porphyrins) has been relatively slow, but the recent isolation of new reduced porphyrins, such as the physiologically active marine pigment bonellin" and sirohydrochlorin (an intermediate in vitamin B12 biosynthesis) is likely to stimulate attempts to synthesize these compounds directly from partially reduced open chain precursors rather than by reduction of preformed porphyrins (see Section 11). Considerable progress has already been made in the development of new methods for synthesizing the partially reduced bile pigments (Section 9). 

The complete structural elucidation of 110 by means of spectroscopic methods and biogenetic considerations was not accomplished until Battersby et al (68) and Bykhovsky et al (69) were able to isolate factor II (sirohydrochlorin) (108) from bacteria producing vitamin B12. Factor II (108) is the metal-free isobacteriochlorin chromophore of siroheme. The reduced forms of factor II (108) and of the subsequently discovered factor III (109) were identified, together with factor I (65), as the first links in the biosynthetic chain from uroporphyrinogen III (14) to vitamin B12 (4) (11). The vitamin B12 biosynthesis will be dealt with in more detail in a later section (see section 9). Factor III (109) differs from factor II (108) by virtue of an additional methyl group in the methine position 20. 

As already mentioned the investigation of vitamin B12 biosynthesis has brought several new hydroporphyrinoid structures to light which... 

On prolonged incubation trimethylpyrrocorphine (136) is formed by over methylation 12a,d). The product of the methylation does not act as an intermediate in the biosynthesis of vitamin B12. The so-called compound-4 (137) is also an over methylated product formed in the vitamin B12 biosynthesis, which is formed with an over expressed methyltransferase (cbi F) from Salmonella typhimurum 87). Compound-4 (137) is closely related to factor S3 (140) (SS). 

Progress of biological action in enzymatic methyl transfer and rearrangement reactions, medicinal aspects, structure and reactivity, and biosynthesis of vitamin B12 and B 12-coenzymes was very recently comprehensively presented at the 4 European Symposium on Vitamin Bi2 and B 12-Proteins and reviewed in an excellent monograph (70). Therefore it is intended with this contribution to address mainly results from research in the field of vitamin B12 biosynthesis. The procedure makes sense because of two reasons. First, many of the biosynthetic intermediates are closely related to hydroporphyrinoid structures discussed in previous sections and second, reactions of the biosynthetic pathway concern the chemistry of the hydroporphyrinoid and corrinoid frameworks involved, whereas the biochemical reactivity of vitamin B12 is mainly restricted to the central cobalt ion of the corrin macrocycle. 

A milestone in vitamin B12 biosynthesis was the discovery of the chlorin factor I (65) by Muller 43, 44) and Arigoni (44) and of the isobacteriochlorin factor II (108) by Bykhovsky (69) and Battersby 68, 69). The reduced forms of factor I (65) and factor II (108) named as precorrin-1 and precorrin-2 were then identified as biosynthetic precursors of vitamin B12 (4). 

Arigoni D, Imfeld M (1979) Factor I ex Clostridium tetanomorphum Proof of Structure and Relationship to Vitamin B12 Biosynthesis. In Zagalak B, Friedrich W (eds) Vitamin B12. de Gruyter, Berlin, New York, p 315... 

Thibaut D, Blanche F, Cameron B, Crouzet J, Debussche L, Remy E, Vuilhorgne M (1998) Vitamin B12 Biosynthesis in Pseudomonas denitrificans. In Krautler B, Arigoni D, Golding BT (eds) Vitamin B12 and Bi2-Proteins. Wiley - VCH, Weinheim... 

Finally, three strains of Lactobacillus reuteri have been used for GEMM reconstrac-tion. Lactobacillus reuteri JCMl 12 had been used for medium optimization to enhance vitamin B12 biosynthesis by insertion of the biosynthetic pathway from Lactobacillus plantarum WCFSl (Santos et al 2008). Furthermore, two isolates derived from breast milk have been used for metabolic model reconstructions (Saulnier et al 2011). Lactobacillus reuteri strain 55730 has been identified as an important probiotic strain, and hence efforts were made to identify its functional properties via the integration of omics data, in particular, the amino acid biosynthesis capacity and vitamin production were detailed thanks to the model and proposed as part of traits enhancing probiotic effects. Such study represents an important step toward a metagenome-scale model and its application in industrial fermentations (Branco Dos Santos, De Vos, Teusink, 2013). 

The same method has been applied in the synthesis of the western building block 1636 of vitamin B12, relevant to vitamin B12 biosynthesis. The original cyano group is reduced to an amino group, this is formylated, the resulting formamide is dehydrated with phosphoryl chloride forming the isocyanide, which is reductively cleaved [1221], For the dehydration of the formamide with phosphoryl chloride, l,8-bis(dimethylamino)naphthalene was chosen as an auxiliary base. 

Ibragimova et al., 1971), excess of substrate (Ibragimova and Saccharova, 1972) can impair the coupling between energetic and constructive processes, so that a greater fraction of metabolites such as ATP, NAD, FAD can be utilized for vitamin B12 biosynthesis. 

Baranova NA and Vorobjeva LI (1971) Influence of peptides on vitamin B12 biosynthesis in Propionibacterium shermanii. Nauchn Dokl Vys Shkoly Biol Nauki 3 97-99... 

Bykhovsky VY, Zaitseva NI and Polulach OV (1987) Biosynthesis of porphyrins by microorganisms. Prikl Biokhim Mikrobiol 23 725-739 Bykhovsky VY, Demain AL and Zaitseva NI (1997) The crucial contribution of starved resting cells to the elucidation of the pathway of vitamin B12 biosynthesis. Crit Rev Biotechnol 17 21-37... 

Ford SH and Friedmann HC (1976) Vitamin B12 biosynthesis in vitro formation of cobinamide from cobyric acid and L-threonine. Arch Biochem Biophys 175 121-130 Forrest WW and Walker DJ (1964) Change in entropy during bacterial metabolism. Nature 20L49-52... 

Silverman M and Werkman CH (1939) Adaptation of the propionic acid bacteria to vitamin Bi synthesis including method of assay. J Bacteriol 38 25-32 Siu PML and Wood HG (1962) Phosphoenolpyruvic carboxytransphosphorylase, a CO2 fixation enzyme from propionic acid bacteria. J Biol Chem 237 3044-3051 Sizova AV and Arkadjeva ZA (1968) Propionic acid bacteria of rumen and their capacity for vitamin B12 biosynthesis. Mikrobiol Sintez 10 8-13... 

Yeliseev AA, Pushkin AV, Zaitseva NI, Evstigneeva ZG, Bykhovsky VY and Kretovich WL (1986b) Glutamine as the source of amide groups in vitamin B12 biosynthesis. Biochim Biophys Acta 880 131-138... 

If you were to look at the steps of vitamin B12 biosynthesis, you would see exactly the same kinds of reactions we ve been seeing throughout the text— nucleophilic substitutions, eliminations, aldol reactions, nucleophilic acyl substitutions, and so forth. There are, of course, some complexities, but the fundamental mechanisms of organic chemistry remain the same, whether in the laboratory with smaller molecules or in organisms with larger molecnles. 

Any pathway to vitamin B12 biosynthesis therefore requires that (0 one animomethyl terminus of the eight ALA units involved in the biosynthesis be lost, and (ii)that seven C-methyl groups be introduced by methionine-two in ring A, one in each of rings b, c, and D, and one in each of the two meso-positions (C-5 and C-15). 

Vitamin 6 2 under aerobic conditions. Glycerol dehydratase (dhaB) is highly sensitive to oxygen. Celinska (2011) discovered that the expression of the dhaB operon is suppressed if the oxygen levels are high in the culture medium. Thus it leads to the excess formation of by-products like lactic acid, acetic acid, and ethanol, respectively, and consequently a very low yield of 3-HP. It was reported that coenzyme Bj2 is not synthesized under aerobic conditions. 3-HP production is carried out imder (micro) aerobic (or) anaerobic conditions only. The introduction of vitamin B12 in recombinant strains is very difficult because more than 20 genes of vitamin B12 biosynthesis pathways need to be expressed in E. coli (Kumar et ak, 2014). 

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