KEGG   PATHWAY: rn00780
Entry
rn00780                     Pathway                                
Name
Biotin metabolism
Description
Biotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase. Mammals cannot synthesize biotin, while in bacteria, fungi, and plants it is synthesized from pimelate thioester through different pathways. In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with the methylation to malonyl-ACP methyl ester, followed by the fatty acid chain elongation cycle to form pimeloyl-ACP methyl ester, which is then demethylated to form pimeloyl-ACP [MD:M00572]. Pimeloyl-ACP is converted to biotin through the final four steps in the biotin bicyclic ring assembly, which are conserved among biotin-producing organisms [MD:M00123]. In B. subtilis, biotin is derived from pimeloyl-ACP formed by oxidative cleavage of long-chain acyl-ACPs [MD:M00573]. Some bacteria synthesize biotin from pimeloyl-CoA derived from pimelate [MD:M00577]. Biotin is covalently attached to biotin-dependent carboxylase by biotin protein ligase, also known as holocarboxylase synthase in mammals, to form an active holocarboxylase. After degradation of the biotinylated carboxylase into biocytin, it is further degraded by biotinidase to release free biotin, which is recycled in holocarboxylase synthesis. Biotin is catabolized by beta-oxidation of the valeric acid side chain or oxidation of sulfur in the heterocyclic ring.
Class
Metabolism; Metabolism of cofactors and vitamins
Pathway map
rn00780  Biotin metabolism
rn00780

Module
M00123  Biotin biosynthesis, pimeloyl-ACP/CoA => biotin [PATH:rn00780]
M00572  Pimeloyl-ACP biosynthesis, BioC-BioH pathway, malonyl-ACP => pimeloyl-ACP [PATH:rn00780]
M00573  Biotin biosynthesis, BioI pathway, long-chain-acyl-ACP => pimeloyl-ACP => biotin [PATH:rn00780]
M00577  Biotin biosynthesis, BioW pathway, pimelate => pimeloyl-CoA => biotin [PATH:rn00780]
M00950  Biotin biosynthesis, BioU pathway, pimeloyl-ACP/CoA => biotin [PATH:rn00780]
Other DBs
GO: 0006768
Reaction
R01074  biotin:CoA ligase (AMP-forming); biotin:apo-[carboxylase] ligase (AMP-forming); ATP:biotin adenylyltransferase
R01077  N6-D-biotinyl-L-lysine amidohydrolase
R01078  dethiobiotin:sulfur sulfurtransferase
R03182  7,8-diaminononanoate:carbon-dioxide cyclo-ligase
R03209  6-carboxyhyxanoate:CoA ligase (AMP-forming)
R03210  pimeloyl-CoA:L-alanine C-carboxyhexanoyltransferase (decarboxylating)
R03231  S-adenosyl-L-methionine:8-amino-7-oxononanoate aminotransferase
R03762  biotin:CoA ligase (AMP-forming); biotinyl-5'-AMP:CoA biotinyltransferase
R04869  
R05145  biotinyl-5'-AMP:apo-[carboxylase] ligase (AMP-forming)
R09543  S-adenosyl-L-methionine:malonyl-[acyl-carrier protein] O-methyltransferase
R09725  pimeloyl-[acyl-carrier protein]-methyl-ester hydrolase
R10115  malonyl-[acyl-carrier protein]-methyl-ester:malonyl-[acyl-carrier protein] C-acyltransferase
R10116  3-hydroxyglutaryl-[acp]-methyl-ester:NADP+ oxidoreductase
R10117  3-hydroxyglutaryl-[acp]-methyl-ester hydro-lyase
R10118  glutaryl-[acp]-methyl-ester:NADP+ oxidoreductase
R10119  glutaryl-[acp]-methyl-ester:malonyl-[acyl-carrier protein] C-acyltransferase (decarboxylating)
R10120  3-hydroxypimeloyl-[acp]-methyl-ester:NADP+ oxidoreductase
R10121  3-hydroxypimeloyl-[acp]-methyl-ester hydro-lyase
R10122  pimelyl-[acyl-carrier protein]-methyl-ester:NADP+ oxidoreductase
R10123  acyl-[acyl-carrier protein],reduced-flavodoxin:oxygen oxidoreductase (pimeloyl-[acyl-carrier protein] forming)
R10124  pimeloyl-[acyl-carrier protein]:L-alanine C-pimeloyltransferase (decarboxylating)
R10127  biotin:NADP+ S-oxidoreductase (biotin S-oxide-forming)
R10699  L-lysine:8-amino-7-oxononanoate aminotransferase
R12934  
R12935  8-amino-7-oxononanoate:[protein]-L-lysine aminotransferase (N-carboxylating)
R13517  spermidine:8-amino-7-oxononanoate aminotransferase
Compound
C00047  L-Lysine
C00086  Urea
C00120  Biotin
C01037  7,8-Diaminononanoate
C01063  Pimeloyl-CoA
C01092  8-Amino-7-oxononanoate
C01209  Malonyl-[acyl-carrier protein]
C01894  Biotinyl-CoA
C01909  Dethiobiotin
C02656  Pimelate
C05552  Biocytin
C05921  Biotinyl-5'-AMP
C06250  Holo-[carboxylase]
C19673  Malonyl-[acp] methyl ester
C19845  Pimeloyl-[acyl-carrier protein]
C19846  Pimeloyl-[acyl-carrier protein] methyl ester
C20372  3-Ketoglutaryl-[acp] methyl ester
C20373  3-Hydroxyglutaryl-[acp] methyl ester
C20374  Enoylglutaryl-[acp] methyl ester
C20375  Glutaryl-[acp] methyl ester
C20376  3-Ketopimeloyl-[acp] methyl ester
C20377  3-Hydroxypimeloyl-[acp] methyl ester
C20378  Enoylpimeloyl-[acp] methyl ester
C20384  Bisnorbiotin
C20385  Tetranorbiotin
C20386  Biotin sulfoxide
C20387  Biotin sulfone
C20683  Long-chain acyl-[acyl-carrier protein]
C22458  8-Amino-7-(carboxyamino)nonanoate
Reference
PMID:21437340
  Authors
Lin S, Cronan JE
  Title
Closing in on complete pathways of biotin biosynthesis.
  Journal
Mol Biosyst 7:1811-21 (2011)
DOI:10.1039/c1mb05022b
Reference
PMID:22965231
  Authors
Lin S, Cronan JE
  Title
The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis.
  Journal
J Biol Chem 287:37010-20 (2012)
DOI:10.1074/jbc.M112.410290
Reference
PMID:20693992
  Authors
Lin S, Hanson RE, Cronan JE
  Title
Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
  Journal
Nat Chem Biol 6:682-8 (2010)
DOI:10.1038/nchembio.420
Reference
PMID:21435937
  Authors
Cronan JE, Lin S
  Title
Synthesis of the alpha,omega-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway.
  Journal
Curr Opin Chem Biol 15:407-13 (2011)
DOI:10.1016/j.cbpa.2011.03.001
Reference
PMID:11368323
  Authors
Stok JE, De Voss J
  Title
Expression, purification, and characterization of BioI: a carbon-carbon bond cleaving cytochrome P450 involved in biotin biosynthesis in Bacillus subtilis.
  Journal
Arch Biochem Biophys 384:351-60 (2000)
DOI:10.1006/abbi.2000.2067
Reference
PMID:18838690
  Authors
Cryle MJ, Schlichting I
  Title
Structural insights from a P450 Carrier Protein complex reveal how specificity is achieved in the P450(BioI) ACP complex.
  Journal
Proc Natl Acad Sci U S A 105:15696-701 (2008)
DOI:10.1073/pnas.0805983105
Reference
PMID:8763940
  Authors
Bower S, Perkins JB, Yocum RR, Howitt CL, Rahaim P, Pero J
  Title
Cloning, sequencing, and characterization of the Bacillus subtilis biotin biosynthetic operon.
  Journal
J Bacteriol 178:4122-30 (1996)
DOI:10.1128/JB.178.14.4122-4130.1996
Reference
PMID:1445232
  Authors
Ploux O, Soularue P, Marquet A, Gloeckler R, Lemoine Y
  Title
Investigation of the first step of biotin biosynthesis in Bacillus sphaericus. Purification and characterization of the pimeloyl-CoA synthase, and uptake of pimelate.
  Journal
Biochem J 287 ( Pt 3):685-90 (1992)
DOI:10.1042/bj2870685
Reference
PMID:12368242
  Authors
Rodionov DA, Mironov AA, Gelfand MS
  Title
Conservation of the biotin regulon and the BirA regulatory signal in Eubacteria and Archaea.
  Journal
Genome Res 12:1507-16 (2002)
DOI:10.1101/gr.314502
Reference
PMID:11320134
  Authors
Sullivan JT, Brown SD, Yocum RR, Ronson CW
  Title
The bio operon on the acquired symbiosis island of Mesorhizobium sp. strain R7A includes a novel gene involved in pimeloyl-CoA synthesis.
  Journal
Microbiology 147:1315-22 (2001)
DOI:10.1099/00221287-147-5-1315
Reference
PMID:12039741
  Authors
Entcheva P, Phillips DA, Streit WR
  Title
Functional analysis of Sinorhizobium meliloti genes involved in biotin synthesis and transport.
  Journal
Appl Environ Microbiol 68:2843-8 (2002)
DOI:10.1128/AEM.68.6.2843-2848.2002
Reference
PMID:19319844
  Authors
Zempleni J, Wijeratne SS, Hassan YI
  Title
Biotin.
  Journal
Biofactors 35:36-46 (2009)
DOI:10.1002/biof.8
Reference
PMID:9022537
  Authors
Zempleni J, McCormick DB, Mock DM
  Title
Identification of biotin sulfone, bisnorbiotin methyl ketone, and tetranorbiotin-l-sulfoxide in human urine.
  Journal
Am J Clin Nutr 65:508-11 (1997)
DOI:10.1093/ajcn/65.2.508
Reference
PMID:5775781
  Authors
Iwahara S, McCormick DB, Wright LD, Li HC
  Title
Bacterial degradation of biotin. 3. Metabolism of 14C-carbonyl-labeled biotin.
  Journal
J Biol Chem 244:1393-8 (1969)
Reference
PMID:2180922
  Authors
Pierson DE, Campbell A
  Title
Cloning and nucleotide sequence of bisC, the structural gene for biotin sulfoxide reductase in Escherichia coli.
  Journal
J Bacteriol 172:2194-8 (1990)
DOI:10.1128/JB.172.4.2194-2198.1990
Reference
PMID:15601707
  Authors
Ezraty B, Bos J, Barras F, Aussel L
  Title
Methionine sulfoxide reduction and assimilation in Escherichia coli: new role for the biotin sulfoxide reductase BisC.
  Journal
J Bacteriol 187:231-7 (2005)
DOI:10.1128/JB.187.1.231-237.2005
Reference
PMID:374979
  Authors
del Campillo-Campbell A, Dykhuizen D, Cleary PP
  Title
Enzymic reduction of d-biotin d-sulfoxide to d-biotin.
  Journal
Methods Enzymol 62:379-85 (1979)
DOI:10.1016/0076-6879(79)62244-9
Reference
PMID:9013576
  Authors
Pollock VV, Barber MJ
  Title
Biotin sulfoxide reductase. Heterologous expression and characterization of a functional molybdopterin guanine dinucleotide-containing enzyme.
  Journal
J Biol Chem 272:3355-62 (1997)
DOI:10.1074/jbc.272.6.3355
Reference
PMID:15366932
  Authors
Nelson KJ, Rajagopalan KV
  Title
Studies on the interaction of NADPH with Rhodobacter sphaeroides biotin sulfoxide reductase.
  Journal
Biochemistry 43:11226-37 (2004)
DOI:10.1021/bi0490845
Reference
PMID:16299174
  Authors
Pinon V, Ravanel S, Douce R, Alban C
  Title
Biotin synthesis in plants. The first committed step of the pathway is catalyzed by a cytosolic 7-keto-8-aminopelargonic acid synthase.
  Journal
Plant Physiol 139:1666-76 (2005)
DOI:10.1104/pp.105.070144
Related
pathway
rn00061  Fatty acid biosynthesis
rn00310  Lysine degradation
rn00960  Tropane, piperidine and pyridine alkaloid biosynthesis
KO pathway
ko00780   

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