Corrin biosynthesis

Uroporphyrinogen I (16c), a constitutional isomer of uroporphyrinogen III, also plays no direct role in porphyrin and corrin biosynthesis, but this unnatural substrate is methylated to give 17c10c f in the presence of SAM by the methyl transferase of some bacteria. A constitutional type I dihydroisobacteriochlorin can be obtained by methylation of uroporphyrinogen I with methylase Ml. Methyltransferase M1 is able to methylate the unnatural precorrin once more to give the trimethylpyrrocorphin type I.IOc 1... 

Cancer, Topics in Chemical Biology Photosynthesis, Electron Transfer Chemistry in Porphyrin and Corrin Biosynthesis... 

Akhtar, M., Jordan, P. M. Porphyrin, chlorophyll and corrin biosynthesis. In Comprehensive Organic Chemistry, Vol. 5, Biological Compounds, pp. 1121-1166. Pergamon Press, Oxford 1979... 

Uroporphyrinogen III (uro gen III) lies at the branching point of porphyrin and corrin biosynthesis. Down one path, following initial decarboxylation, both chloro-... 

The tautomerization of porphyrinogens to pyrrocorphins has been reported in detail in connection with the synthesis of chlorins (sec Section 1.2.1.3.), baeteriochlorins (see Section 1.3.1.) and isobacteriochlorins (see Section 1.4.1.3.). Therefore, only the porphyrinogen-pyrrocorphin tautomerization of uroporphyrinogen I octacarbonitrile 8- 96 will be described as it is of importance regarding the biosynthesis and a possible prebiotic formation of corrins.la,b-2 A major problem concerned with using this approach synthetically is the number of possible diastereomeric products (4 in a 1 1 1 1 ratio) obtained in the reaction and also the formation of isobacteriochlorin diastereomers 10. 

The tetramerization of suitable monopyrroles is one of the simplest and most effective approaches to prepare porphyrins (see Section 1.1.1.1.). This approach, which is best carried out with a-(hydroxymethyl)- or ot-(aminomethyl)pyrroles, can be designated as a biomimetic synthesis because nature also uses the x-(aminomethyl)pyrrole porphobilinogen to produce uroporphyrinogen III. the key intermediate in the biosynthesis of all kinds of naturally occurring porphyrins, hydroporphyrins and corrins. The only restriction of this tetramerization method is the fact that tnonopyrroles with different -substituents form a mixture of four constitutionally isomeric porphyrins named as porphyrins I, II, III, and IV. In the porphyrin biosynthesis starting from porphobilinogen, which has an acetic acid and a propionic acid side chain in the y6-positions, this tetramerization is enzymatically controlled so that only the type III constitutional isomer is formed. 

Vitamin Bu coenzymes, Ann. N.Y. Acad, Set. 112, 547-921 (1964). I. Chemistry, chemical synthesis and biosynthesis of corrin coenzymes II. Enzymic roles of cobinamide coenzymes III. B 12-coenzymes in micro-organisms and animals. 

Naturally, the biosynthesis of cobalamins themselves require delivery of Co ions at a particular point in the reaction scheme. Cobaltochelatase catalyzes the ATP-dependent insertion of Co11 into the corrin ring during the biosynthesis of coenzyme B12 in Pseudomonas denitrifleans. Cobaltochelatase is a heterodimeric enzyme (140 KDA and 450 KDA subunits each inactive in isolation), and the two components have been isolated and purified to homogeneity.1119 The reaction product is divalent cobyrinic acid, demonstrating that hydrogenobyrinic acid and its diamide (255) are precursors of AdoCbl. 

The most exciting research is yet to be performed on 13C NMR of the corrin enzymes. This could be accomplished by biosynthesis of C-13 enriched samples of biologically active B12 derivatives followed by their incorporation into enzymes. Since it has been shown that 13C-spectra of corrinoids are well resolved, and sensitive to small changes in the molecular conformation, then one could hope to get quite detailed information pertinent to the binding of B12 and to the mechnism of enzyme catalysis. 

Certain strictly anaerobic bacteria and lactic acid bacteria apparently do not contain heme compounds. In the first named organisms this cannot be ascribed to a failure to perform the first step in porphyrin biosynthesis since Clostridia are notorious for production of the porphyrin-like nucleus (corrin) which occurs in vitamin B12 (7, 43). 

Several macrocyclic ligands are shown in Figure 2. The porphyrin and corrin ring systems are well known, the latter for the cobalt-containing vitamin Bi2 coenzymes. Of more recent interest are the hydroporphyrins. Siroheme (an isobacteriochlorin) is the prosthetic group of the sulfite and nitrite reductases which catalyze the six-electron reductions of sulfite and nitrite to H2S and NH3 respectively. The demetallated form of siroheme, sirohydrochlorin, is an intermediate in the biosynthesis of vitamin Bi2, and so links the porphyrin and corrin macrocycles. Factor 430 is a tetrahydroporphyrin, and as its nickel complex is the prosthetic group of methyl coenzyme M reductase. F430 shows structural similarities to both siroheme and corrin. 

The synthetic procedure involving ring contraction of hydroporphyrins has been applied only to the preparation of corrin complexes [78] and it has been inspired by the studies on the biosynthesis of Vitamin B12. The macroring precursor is the hexahydroporphyrin shown in Fig. 29. 

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). 

Although the corrin nucleus of vitamin Bl2 (1) contains nine asymmetric carbon atoms, it is constructed by nature from achiral building blocks, and the first macrocyclic intermediate in the biosynthetic pathway, uroporphyrinogen III (60), is also achiral. Since uroporphyrinogen III is a common precursor of all tetrapyrrolic macrocycles, it is convenient to discuss its biosynthesis first and then summarize the known facts of the transformation of uroporphyrinogen III to the corrin nucleus. 

During the last few years many interesting details of the biosynthesis of corrins and porphyrins have been discovered. The methods by which nature builds up such complex molecules are sometimes conventional, even monotonous, and sometimes surprising. Monotonous are, for example, the repeated reductive methylations of the four pyrrole rings with the same regio- and stereospecificity, surprising the introduction into posidon C-20 of a methyl group which is extruded later as acetate. 

The unmatched complex structure of the low-molecular weight natural product vitamin Bn posed a challenge to synthetic chemistry, which was met in the early 1970s by Eschemnoser and by Woodward and their coworkers. The biosynthesis of the structure of natural cobalt-corrins is no less intricate and facets of its pathways still remain to be uncovered (see section 2.3). 

The corrins are related to the natural porphyrins by both their structure and their biosynthesis. Besides its linearly... 

The natural corrinoids are made exclusively by microorganisms, which are also exploited on a large scale for the industrial production of vitamin B12. The biosynthesis of the corrin ligand branches off from that of the other porphinoids at their common tetrapyrrolic intermediate, uroporphyrinogen III, and has been studied both in aerobic and in anaerobic... 

Because of its immense scope, a detailed description of corrins (and vitamin B12) will not be presented here. The reader is instead referred to reviews of B12 chemistry and its biosynthesis that have appeared recently. Further, because they are more directly related to the corrins than are the corroles, the chemistry of the dehydrocorrins will not be discussed here. Also not included in this review are the so-called artificial porphyrins of Floriani, et al. (e.g., 2.5), since it is deemed by these authors in their review that these macrocycles are more dehydrocorrin-like than corrole-like in their nature. Other systems omitted here include the spiro porphyrins of Battersby and coworkers, the tetraphosphole macrocycles of Mathey and coworkers and the tetrapyrrolic systems of Bartczak and Smith and co-workers. Thus, the emphasis will be on those contracted porphyrins that are most removed, in structural and chemical terms, from the macrocyclic unit found in coenzyme B12 and its analogs. 

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