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Aquifex aeolicus VF5 Pathway: biotin biosynthesis from 8-amino-7-oxononanoate I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Synonyms: biotin biosynthesis from 7-keto-8-aminopelargonate

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Vitamins Biosynthesis Biotin Biosynthesis

Pathway Summary from MetaCyc:
General Background

Biotin is a water soluble, heterocyclic cofactor for a small number of enzymes that facilitate the transfer of CO2 during carboxylation, decarboxylation, and transcarboxylation reactions involved in fatty acid and carbohydrate metabolism [Shellhammer90, Picciocchi01, Alban00]. The biotin-requiring enzymes identified so far (including acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase, and pyruvate carboxylase) play essential roles in cell metabolism [Patton96]. Biotin may also have functions in metabolism other than its mere catalytic role as an enzyme cofactor. It has been shown that biotin also carries out non-catalytic functions in the expression of methylcrotonyl-CoA carboxylase in Arabidopsis biotin-auxotroph mutants, by modulating and regulating gene expression [Che03].

Biotin biosynthesis is found in plants, bacteria, and certain fungi. Although animals and most fungi cannot synthesize their own biotin, a daily intake is required for normal growth and development [Schneider01a]. The biotin biosynthetic pathway has been explored in detail in bacteria. Sequencing analysis and some experimental evidence suggests that the steps in bacterial biotin synthesis are conserved in plants [Schneider01a].

About This Pathway

Biotin consists of two fused heterocyclic rings and a pentanoate side chain, derived from a pimelate-like structure. The early steps of the pathway are responsible for the synthesis of the precursor pimelate moiety, and are described in the pathways 8-amino-7-oxononanoate biosynthesis I and 8-amino-7-oxononanoate biosynthesis III. The late steps of the pathway, which are responsible for forming the two rings in the structure of biotin, are described here.

The first step in this part of the pathway involves the unusual use of the common methyl-group donor S-adenosyl-L-methionine as an amino-group donor, a reaction catalyzed by the bioA-encoded 7,8-diaminopelargonic acid synthase [Stoner75a, Stoner75, Eliot02]. This product of this reaction, 7,8-diaminopelargonate, is the target of a unique carboxylase, the bioD-encoded dethiobiotin synthetase. This enzye catalyzes the first ring closure by a carboxylation reaction that does not require biotin as a prosthetic group, forming dethiobiotin [Krell70].

The ultimate step in the pathway is catalyzed by biotin synthase, encoded by bioB. This enzyme inserts a sulfur atom between C6 and C9 of dethiobiotin in a S-adenosyl-L-methionine-dependent reaction. It has not been possible to reconstitute a catalytic reaction of this enzyme in vitro, and there is some uncertainty regarding the reaction mechanism, cofactor requirements, and the source of the sulfur atom [Jarrett05]. However, recent experiments have suggested that a [2Fe-2S] iron-sulfur cluster of the enzyme is the source of the sulfur atom. Consistent with its proposed role as the sulfur donor, degradation of the [2Fe-2S] cluster [Jameson04] as well as exchange of sulfur atoms between the [2Fe-2S] and [4Fe-4S] clusters [Tse06] is observed during turnover of the enzyme.

Recently detailed analysis of biotin biosynthetic genes was done with several additional bacterial species. There is much variation in the organization of the genes involved: In some cases all of the bio genes are organized within a single transcription unit (such as Bacillus subtilis [Bower96] and Mesorhizobium loti [Sullivan01]), while in other cases the genes are organized in multiple operons, sometimes at different locations in the chromosome. Some organisms even lack some of the genes - for example, Corynebacterium glutamicum seems to lack the bioC, bioH, and bioF genes [Hatakeyama93].

The difference between the biosynthetic pathways of Gram-negative bacteria (biotin biosynthesis I) and Gram-positive bacteria (biotin biosynthesis II) is upstream of the precursor 8-amino-7-oxononanoate. Gram-positive bacteria generate 8-amino-7-oxononanoate from pimelate as described in 8-amino-7-oxononanoate biosynthesis III, while in Gram-negative bacteria 8-amino-7-oxononanoate is synthesized from malonyl-CoA in a pathway described in 8-amino-7-oxononanoate biosynthesis I [Lin10].

About This Pathway in Plants

The biotin pathway has been investigated using biotin-auxotroph mutants of Arabidopsis thaliana. It could be shown that two enzymes correspond to certain mutations - bioA, which has been shown to encode the enzyme 7,8-diaminopelargonic acid aminotransferase [Patton96], and bio2, which encodes the biotin synthase [Baldet96, Patton98].

Biotin synthase is the only enzyme of the pathway which has been investigated in plants on the molecular level [Baldet96, Baldet97, Picciocchi01, Picciocchi03]. Biotin synthase activity could be clearly demonstrated in Arabidopsis utilizing the synthase and accessory proteins from Escherichia coli [Picciocchi01]. It has been shown that mitochondrial components are necessary for the function of the enzyme, acting similar to the flavodoxin reduction system found in Escherichia coli. The mitochondrial components identified were adrenodoxin, adrenodoxin reductase and cystein desulfurase (Nfs1) which proved to be essential for the plant biotin synthase reaction and accommodates the cellular location of the enzyme [Picciocchi03].

Pathway Evidence Glyph:

Key to pathway glyph edge colors: ?

  An enzyme catalyzing this reaction is present in this organism
  The reaction and any enzyme that catalyzes it (if one has been identified) is unique to this pathway

Credits:
Created in MetaCyc 31-Jan-1995 by Riley M , Marine Biological Laboratory
Revised in MetaCyc 29-Sep-2005 by Caspi R , SRI International
Imported from MetaCyc 08-Aug-2014 by Subhraveti P , SRI International


References

Alban00: Alban C, Job D, Douce R (2000). "Biotin metabolism in plants." Annu Rev Plant Physiol Plant Mol Biol 51;17-47. PMID: 15012185

Baldet96: Baldet P, Ruffet ML (1996). "Biotin synthesis in higher plants: isolation of a cDNA encoding Arabidopsis thaliana bioB-gene product equivalent by functional complementation of a biotin auxotroph mutant bioB105 of Escherichia coli K12." C R Acad Sci III 319(2);99-106. PMID: 8680961

Baldet97: Baldet P, Alban C, Douce R (1997). "Biotin synthesis in higher plants: purification and characterization of bioB gene product equivalent from Arabidopsis thaliana overexpressed in Escherichia coli and its subcellular localization in pea leaf cells." FEBS Lett 419(2-3);206-10. PMID: 9428635

Bower96: Bower S, Perkins JB, Yocum RR, Howitt CL, Rahaim P, Pero J (1996). "Cloning, sequencing, and characterization of the Bacillus subtilis biotin biosynthetic operon." J Bacteriol 1996;178(14);4122-30. PMID: 8763940

Che03: Che P, Weaver LM, Wurtele ES, Nikolau BJ (2003). "The role of biotin in regulating 3-methylcrotonyl-coenzyme a carboxylase expression in Arabidopsis." Plant Physiol 131(3);1479-86. PMID: 12644697

Eliot02: Eliot AC, Sandmark J, Schneider G, Kirsch JF (2002). "The dual-specific active site of 7,8-diaminopelargonic acid synthase and the effect of the R391A mutation." Biochemistry 41(42);12582-9. PMID: 12379100

Hatakeyama93: Hatakeyama K, Hohama K, Vertes AA, Kobayashi M, Kurusu Y, Yukawa H (1993). "Genomic organization of the biotin biosynthetic genes of coryneform bacteria: cloning and sequencing of the bioA-bioD genes from Brevibacterium flavum." DNA Seq 4(3);177-84. PMID: 8161820

Jameson04: Jameson GN, Cosper MM, Hernandez HL, Johnson MK, Huynh BH (2004). "Role of the [2Fe-2S] cluster in recombinant Escherichia coli biotin synthase." Biochemistry 43(7);2022-31. PMID: 14967042

Jarrett05: Jarrett JT (2005). "Biotin synthase: enzyme or reactant?." Chem Biol 12(4);409-10. PMID: 15850974

Krell70: Krell K, Eisenberg MA (1970). "The purification and properties of dethiobiotin synthetase." J Biol Chem 1970;245(24);6558-66. PMID: 4921568

Lin10: Lin S, Hanson RE, Cronan JE (2010). "Biotin synthesis begins by hijacking the fatty acid synthetic pathway." Nat Chem Biol 6(9);682-8. PMID: 20693992

Patton96: Patton DA, Volrath S, Ward ER (1996). "Complementation of an Arabidopsis thaliana biotin auxotroph with an Escherichia coli biotin biosynthetic gene." Mol Gen Genet 251(3);261-6. PMID: 8676868

Patton98: Patton DA, Schetter AL, Franzmann LH, Nelson K, Ward ER, Meinke DW (1998). "An embryo-defective mutant of arabidopsis disrupted in the final step of biotin synthesis." Plant Physiol 116(3);935-46. PMID: 0009501126

Picciocchi01: Picciocchi A, Douce R, Alban C (2001). "Biochemical characterization of the Arabidopsis biotin synthase reaction. The importance of mitochondria in biotin synthesis." Plant Physiol 127(3);1224-33. PMID: 11706201

Picciocchi03: Picciocchi A, Douce R, Alban C (2003). "The plant biotin synthase reaction. Identification and characterization of essential mitochondrial accessory protein components." J Biol Chem 278(27);24966-75. PMID: 12714594

Schneider01a: Schneider G, Lindqvist Y (2001). "Structural enzymology of biotin biosynthesis." FEBS Lett 495(1-2);7-11. PMID: 11322938

Shellhammer90: Shellhammer J, Meinke D (1990). "Arrested Embryos from the biol Auxotroph of Arabidopsis thaliana Contain Reduced Levels of Biotin." Plant Physiol. 93; 1162-1167.

Stoner75: Stoner GL, Eisenberg MA (1975). "Biosynthesis of 7, 8-diaminopelargonic acid from 7-keto-8-aminopelargonic acid and S-adenosyl-L-methionine. The kinetics of the reaction." J Biol Chem 1975;250(11);4037-43. PMID: 1092682

Stoner75a: Stoner GL, Eisenberg MA (1975). "Purification and properties of 7, 8-diaminopelargonic acid aminotransferase." J Biol Chem 1975;250(11);4029-36. PMID: 1092681

Sullivan01: Sullivan JT, Brown SD, Yocum RR, Ronson CW (2001). "The bio operon on the acquired symbiosis island of Mesorhizobium sp. strain R7A includes a novel gene involved in pimeloyl-CoA synthesis." Microbiology 147(Pt 5);1315-22. PMID: 11320134

Tse06: Tse Sum Bui B, Mattioli TA, Florentin D, Bolbach G, Marquet A (2006). "Escherichia coli biotin synthase produces selenobiotin. Further evidence of the involvement of the [2Fe-2S]2+ cluster in the sulfur insertion step." Biochemistry 45(11);3824-34. PMID: 16533066

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Allison38: Allison, F. E., Minor, F. W. (1938). "Coenzyme R requirements of rhizobia." Soil Sc.i 46:473-483.

Koegl36: Koegl, F., Toennis, B. (1936). "Uber das bios-problem: Darstellung von krystallisiertem Biotin aus eigelb." Z. Physiol. Chem. 242:43-73.

Lardy49: Lardy, H. A., Potter, R. L., Burris, R. H. (1949). "Metabolic functions of biotin I. The role of biotin in bicarbonate utilization by Lactobacillus arabinosis studied with 14C." J Biol Chem 179:721-731.

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lynen61: Lynen, F., Knappe, J., Lorch, E. J., Ringelmann, E., Lachance, J. P. (1961). "Zur biochemischen Funktion des Biotins. 2. Reinigung und Wirkungsweise der beta-methyl-crotonyl-caboxylase." Biochem Z 335:123.

Melville42: Melville, D. B., Moyer, A. W., Hofmann, K., Vigneaud, V. du (1942). "The structure of biotin: the formation of thiophenevaleric acid from biotin." J Biol Chem 146:487-492.

Streit03: Streit WR, Entcheva P (2003). "Biotin in microbes, the genes involved in its biosynthesis, its biochemical role and perspectives for biotechnological production." Appl Microbiol Biotechnol 61(1);21-31. PMID: 12658511

Vigneaud41: Vigneaud, V. du, Melville, D. B., Gyorg,y P. (1941). "Isolation of biotin (vitamin H) from liver." J Biol Chem 140:643-651.

Vigneaud41a: Vigneaud, V. du,, Melville, D. B., Rachele, J. (1941). "The preparation of free crystalline biotin." J Biol Chem 140:763-766.

Wakil58: Wakil SJ, Titchener EB, Gibson DM (1958). "Evidence for the participation of biotin in the enzymic synthesis of fatty acids." Biochim Biophys Acta 29(1);225-6. PMID: 13560478

Wildiers01: Wildiers, E. (1901). "Nouvelle substance indispensable au developpement de la levure." La Cellule 18:313-316.


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