Sirohydrochlorin 20- methyl

In 1973, the first naturally occurring isobacteriochlorin, iron-containing siroheme, was isolated1 from a sulfite reductase of Escherichia coli. Later it was also discovered in sulfite and nitrite reductases of numerous bacteria and plants.2 Iron-free sirohydrochlorins (also called factor II) were discovered in vitamin B12 producing bacteria.3-4 Together with factor III. a sirohydrochlorin methylated in the 20-position, the reduced forms of factor II and factor III were identified as biosynthetic intermediates in the biosynthesis of vitamin B12.5... 

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. 

Starting from uro gen III, methylation occurs, via the enzyme S-adenosyl methionine uro gen III methyl transferase (SUMT), first at C-2 and then at C-7, to give a dihydroisobacteriochlorin (also known as precorrin 2). However, this compound is extremely air sensitive and is rapidly oxidised to give the isobacteriochlorin (or sirohydrochlorin). 

Interestingly, the sirohydrochlorin can chelate iron to give siroheme which is the cofactor for the enz)nnes sulphite and nitrite reductase, used to reduce sulphite to sulphide and nitrite to ammonia, respectively, in certain organisms (e.g. Esherichia coif). Meanwhile, the dihydroisobacteriochlorin undergoes further methylation at the mcse-carbon C-20 to give precorrin-3. The use of the term "precorrin" was introduced by Battersby to denote intermediates on the pathway that precede the formation of the fully formed corrin macrocycle of vitamin B]2- The number suffix denotes how many C-methyl groups have been introduced into uro gen III. 

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. 

The first step of the siroheme branch is the methylation of uroporphyrinogen III to give dihydrosirohydrochlorin (Figure 5.38). This reaction is catalyzed by a SAM-dependent methyltrasferase [138]. The following step is the oxidation step catalyzed by an unidentified oxidase. Completion of this oxidation process produces sirohydrochlorin. Subsequently, sirohydrochlorin FeCh inserts Fe + into sirohydrochlorin to give siroheme. The enzyme involved in this step resembles FeCh, the chelatase involved in the heme branch [139]. 

Finally, in Scheme 14.33, oxidation of precorrin-2 (NAD+/NADH is the cofactor for the use of the enzyme precorrin-2 dehydrogenase, EC 1.3.1.76) yields sirohydro-chlorin, which, with ferrous (Fe ) iron and the enzyme sirohydrochlorin ferrochelatase (EC 4.99.1.4), produces siroheme. If, in place of oxidation, yet another methylation were to occur, precorrin-2 would be converted to precorrin-3A (precorrin-2 C20-methyltransferase, EC 2.1.1.130) and then, after addition methylation, and modification, to cobalamin. 

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