Entry 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 vitaminsBRITE hierarchy
Pathway map Module M00123 Biotin biosynthesis, pimeloyl-ACP/CoA => biotin [PATH:ko00780 ]
M00572 Pimeloyl-ACP biosynthesis, BioC-BioH pathway, malonyl-ACP => pimeloyl-ACP [PATH:ko00780 ]
M00573 Biotin biosynthesis, BioI pathway, long-chain-acyl-ACP => pimeloyl-ACP => biotin [PATH:ko00780 ]
M00577 Biotin biosynthesis, BioW pathway, pimelate => pimeloyl-CoA => biotin [PATH:ko00780 ]
M00950 Biotin biosynthesis, BioU pathway, pimeloyl-ACP/CoA => biotin [PATH:ko00780 ]
Other DBs Orthology K00059 fabG, OAR1; 3-oxoacyl-[acyl-carrier protein] reductase [EC:1.1.1.100 ]
K00647 fabB; 3-oxoacyl-[acyl-carrier-protein] synthase I [EC:2.3.1.41 ]
K00833 bioA; adenosylmethionine---8-amino-7-oxononanoate aminotransferase [EC:2.6.1.62 ]
K01947 birA-coaX; biotin---[acetyl-CoA-carboxylase] ligase / type III pantothenate kinase [EC:6.3.4.15 2.7.1.33 ]
K02170 bioH; pimeloyl-[acyl-carrier protein] methyl ester esterase [EC:3.1.1.85 ]
K02372 fabZ; 3-hydroxyacyl-[acyl-carrier-protein] dehydratase [EC:4.2.1.59 ]
K03524 birA; BirA family transcriptional regulator, biotin operon repressor / biotin---[acetyl-CoA-carboxylase] ligase [EC:6.3.4.15 ]
K08351 bisC; biotin/methionine sulfoxide reductase [EC:1.-.-.-]
K09458 fabF, OXSM, CEM1; 3-oxoacyl-[acyl-carrier-protein] synthase II [EC:2.3.1.179 ]
K09789 bioG; pimeloyl-[acyl-carrier protein] methyl ester esterase [EC:3.1.1.85 ]
K19560 bioK; pimeloyl-[acyl-carrier protein] methyl ester esterase [EC:3.1.1.85 ]
K19561 bioJ; pimeloyl-[acyl-carrier protein] methyl ester esterase [EC:3.1.1.85 ]
K19562 BIO3-BIO1; bifunctional dethiobiotin synthetase / adenosylmethionine---8-amino-7-oxononanoate aminotransferase [EC:6.3.3.3 2.6.1.62 ]
K19563 bioA, bioK; lysine---8-amino-7-oxononanoate aminotransferase [EC:2.6.1.105 ]
K25570 bioU; 8-amino-7-oxononanoate carboxylating dehydrogenase
Compound C01209 Malonyl-[acyl-carrier protein]
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
C20683 Long-chain acyl-[acyl-carrier protein]
C22458 8-Amino-7-(carboxyamino)nonanoate
Reference Authors Lin S, Cronan JE
Title Closing in on complete pathways of biotin biosynthesis.
Journal Reference 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 Reference Authors Lin S, Hanson RE, Cronan JE
Title Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
Journal Reference Authors Cronan JE, Lin S
Title Synthesis of the alpha,omega-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway.
Journal Reference 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 Reference 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 Reference 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 Reference 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 Reference Authors Rodionov DA, Mironov AA, Gelfand MS
Title Conservation of the biotin regulon and the BirA regulatory signal in Eubacteria and Archaea.
Journal Reference 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 Reference Authors Entcheva P, Phillips DA, Streit WR
Title Functional analysis of Sinorhizobium meliloti genes involved in biotin synthesis and transport.
Journal Reference Authors Zempleni J, Wijeratne SS, Hassan YI
Title Biotin.
Journal Reference Authors Zempleni J, McCormick DB, Mock DM
Title Identification of biotin sulfone, bisnorbiotin methyl ketone, and tetranorbiotin-l-sulfoxide in human urine.
Journal Reference 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 Authors Pierson DE, Campbell A
Title Cloning and nucleotide sequence of bisC, the structural gene for biotin sulfoxide reductase in Escherichia coli.
Journal Reference 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 Reference Authors del Campillo-Campbell A, Dykhuizen D, Cleary PP
Title Enzymic reduction of d-biotin d-sulfoxide to d-biotin.
Journal Reference Authors Pollock VV, Barber MJ
Title Biotin sulfoxide reductase. Heterologous expression and characterization of a functional molybdopterin guanine dinucleotide-containing enzyme.
Journal Reference Authors Nelson KJ, Rajagopalan KV
Title Studies on the interaction of NADPH with Rhodobacter sphaeroides biotin sulfoxide reductase.
Journal Reference 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 Related ko00960 Tropane, piperidine and pyridine alkaloid biosynthesis
