Anaerobic synthesis of vitamin B12: characterization of the early steps in the pathway.

The anaerobic biosynthesis of vitamin B12 is slowly being unravelled. Recent work has shown that the first committed step along the anaerobic route involves the sirohydrochlorin (chelation of cobalt into factor II). The following enzyme in the pathway, CbiL, methylates cobalt-factor II to give cobalt-factor III. Recent progress on the molecular characterization of this enzyme has given a greater insight into its mode of action and specificity. Structural studies are being used to provide insights into how aspects of this highly complex biosynthetic pathway may have evolved. Between cobalt-factor III and cobyrinic acid, only one further intermediate has been identified. A combination of molecular genetics, recombinant DNA technology and bioorganic chemistry has led to some recent advances in assigning functions to the enzymes of the anaerobic pathway.

[1]  M. Lindenmeyer,et al.  Aerobic synthesis of vitamin B12: ring contraction and cobalt chelation. , 2005, Biochemical Society transactions.

[2]  H. Williams,et al.  Genetically Engineered Production of 1-Desmethylcobyrinic Acid, 1-Desmethylcobyrinic Acid a,c-Diamide, and Cobyrinic Acid a,c-Diamide in Escherichia coli Implies a Role for CbiD in C-1 Methylation in the Anaerobic Pathway to Cobalamin* , 2005, Journal of Biological Chemistry.

[3]  E. Getzoff,et al.  Structure/function studies on a S-adenosyl-L-methionine-dependent uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis. , 2004, Journal of molecular biology.

[4]  A. Munro,et al.  Characterization of the Cobaltochelatase CbiXL , 2003, Journal of Biological Chemistry.

[5]  H. Schubert,et al.  A Story of Chelatase Evolution , 2003, Journal of Biological Chemistry.

[6]  A. Scott,et al.  Discovering nature's diverse pathways to vitamin B12: a 35-year odyssey. , 2003, The Journal of organic chemistry.

[7]  D. Jahn,et al.  Identification and functional analysis of enzymes required for precorrin-2 dehydrogenation and metal ion insertion in the biosynthesis of sirohaem and cobalamin in Bacillus megaterium. , 2003, The Biochemical journal.

[8]  John F Hunt,et al.  The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase. , 2002, Structure.

[9]  J. Escalante‐Semerena,et al.  The biosynthesis of adenosylcobalamin (vitamin B12). , 2002, Natural product reports.

[10]  J. Rose,et al.  Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters , 2000, Cellular and Molecular Life Sciences CMLS.

[11]  K S Wilson,et al.  Common chelatase design in the branched tetrapyrrole pathways of heme and anaerobic cobalamin synthesis. , 1999, Biochemistry.

[12]  K. Wilson,et al.  Vitamin B12: Insights into Biosynthesis's Mount Improbable , 1999 .

[13]  L. Sumner,et al.  Definition of the redox states of cobalt-precorrinoids: investigation of the substrate and redox specificity of CbiL from Salmonella typhimurium. , 1998, Biochemistry.

[14]  Keith S. Wilson,et al.  The X-ray structure of a cobalamin biosynthetic enzyme, cobalt-precorrin-4 methyltransferase , 1998, Nature Structural Biology.

[15]  S. Nikonov,et al.  Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis. , 1997, Structure.

[16]  C. Roessner,et al.  How corrinoids are synthesized without oxygen: nature's first pathway to vitamin B12. , 1997, Chemistry & biology.

[17]  A. Scott,et al.  Biosynthesis of vitamin B12: factor IV, a new intermediate in the anaerobic pathway. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Scott,et al.  Biosynthesis of vitamin B12: concerning the identity of the two-carbon fragment eliminated during anaerobic formation of cobyrinic acid. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[19]  T. Bobik,et al.  Cobalamin (coenzyme B12): synthesis and biological significance. , 1996, Annual review of microbiology.

[20]  L. Debussche,et al.  Vitamin B12: How the Problem of Its Biosynthesis Was Solved , 1995 .

[21]  A. Battersby.  How nature builds the pigments of life: the conquest of vitamin B12. , 1994, Science.

[22]  A. Scott.  On the Duality of Mechanism of Ring Contraction iv Vitamin B12 Biosysthesis , 1994 .

[23]  L. Debussche,et al.  Parallels and Decisive Differences in Vitamin B12 Biosyntheses , 1993 .

[24]  Harvard Medical School,et al.  Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium , 1993, Journal of bacteriology.

[25]  B. Atshaves,et al.  Timing and mechanistic implications of regiospecific carbonyl oxygen isotope exchange during vitamin B12 biosynthesis , 1991 .

[26]  M. Warren,et al.  Tetrapyrrole assembly and modification into the ligands of biologically functional cofactors. , 1990, Trends in biochemical sciences.

[27]  L. Debussche,et al.  Purification and characterization of S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase from Pseudomonas denitrificans , 1989, Journal of bacteriology.

[28]  F. Leeper,et al.  Biosynthesis of porphyrins and related, macrocycles. Part 28. Development of a pulse labelling method to determine the C-methylation sequence for vitamin B12 , 1987 .

[29]  N H Horowitz,et al.  On the Evolution of Biochemical Syntheses. , 1945, Proceedings of the National Academy of Sciences of the United States of America.