ENTRY       mtr00780                    Pathway
NAME        Biotin metabolism - Medicago truncatula (barrel medic)
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 mtr00780  Biotin metabolism
MODULE      mtr_M00123  Biotin biosynthesis, pimeloyl-ACP/CoA => biotin [PATH:mtr00780]
DBLINKS     GO: 0006768
ORGANISM    Medicago truncatula (barrel medic) [GN:mtr]
GENE        25502219  3-oxoacyl-[acyl-carrier-protein] synthase I, chloroplastic [KO:K09458] [EC:2.3.1.179]
            11411851  LOW QUALITY PROTEIN: 3-oxoacyl-[acyl-carrier-protein] synthase I, chloroplastic [KO:K09458] [EC:2.3.1.179]
            11446734  3-oxoacyl-[acyl-carrier-protein] synthase II, chloroplastic [KO:K09458] [EC:2.3.1.179]
            25486549  3-oxoacyl-[acyl-carrier-protein] synthase II, chloroplastic [KO:K09458] [EC:2.3.1.179]
            25484188  3-oxoacyl-[acyl-carrier-protein] synthase, mitochondrial [KO:K09458] [EC:2.3.1.179]
            25485150  3-oxoacyl-[acyl-carrier-protein] synthase I, chloroplastic [KO:K09458] [EC:2.3.1.179]
            25484124  NADPH-dependent aldehyde reductase-like protein, chloroplastic [KO:K00059] [EC:1.1.1.100]
            11440405  3-oxoacyl-[acyl-carrier-protein] reductase 4 [KO:K00059] [EC:1.1.1.100]
            25499093  NADPH-dependent aldehyde reductase-like protein, chloroplastic [KO:K00059] [EC:1.1.1.100]
            25499094  NADPH-dependent aldehyde reductase-like protein, chloroplastic [KO:K00059] [EC:1.1.1.100]
            11419786  3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ [KO:K02372] [EC:4.2.1.59]
            25493282  3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ [KO:K02372] [EC:4.2.1.59]
            11446620  enoyl-[acyl-carrier-protein] reductase [NADH], chloroplastic-like [KO:K00208] [EC:1.3.1.9 1.3.1.10]
            25498181  enoyl-[acyl-carrier-protein] reductase [NADH], chloroplastic [KO:K00208] [EC:1.3.1.9 1.3.1.10]
            11411786  8-amino-7-oxononanoate synthase isoform X1 [KO:K00652] [EC:2.3.1.47]
            11446047  bifunctional dethiobiotin synthetase/7,8-diamino-pelargonic acid aminotransferase, mitochondrial isoform X1 [KO:K19562] [EC:6.3.3.3 2.6.1.62]
            11439216  biotin synthase, mitochondrial [KO:K01012] [EC:2.8.1.6]
            11411288  biotin--protein ligase 2 [KO:K01942] [EC:6.3.4.9 6.3.4.10 6.3.4.11 6.3.4.15]
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
REL_PATHWAY mtr00061  Fatty acid biosynthesis
            mtr00310  Lysine degradation
            mtr00960  Tropane, piperidine and pyridine alkaloid biosynthesis
KO_PATHWAY  ko00780
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