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Pathway Description
Biotin Metabolism
Escherichia coli ED1a
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2024-12-11
Last Updated: 2025-07-06
Biotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase. In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with a malonyl-[acp] interacting with S-adenosylmethionine through a biotin synthesis protein BioC resulting in an S-adenosylhomocysteine and a malonyl-[acp] methyl ester. The latter compound is then involved in the synthesis of a 3-ketoglutaryl-[acp] methyl ester through a 3-oxoacyl-[acyl-carrier-protein] synthase. The compound 3-ketoglutaryl-[acp] methyl ester is reduced by a NADPH-mediated 3-oxoacyl-[acyl-carrier-protein] reductase resulting in a 3R-hydroxyglutaryl-[acp] methyl ester. It is then dehydrated through a (3R)-hydroxymyristoyl-[acp] dehydratase producing an enoylglutaryl-[acp] methyl ester. enoylglutaryl-[acp] methyl ester is then reduced through an NADPH mediated enoyl-acp-reductase [NADH] resulting in a glutaryl-[acp] methyl ester.
Continuing, glutaryl-[acp] methyl ester interacts with a malonyl-[acp] through a 3-oxoacyl-[acp] synthase 2 resulting in a 3-ketopimeloyl [acp] methyl ester then is further reduced through an NADPH 3-oxoacyl [acp] reductase producing a 3-hydroxypimeloyl-[acp] methyl ester and then dehydrated by (3R)-hydroxymyristoyl-[acp] dehydratase to produce an enoylpimeloyl-[acp] methyl ester. The product is then reduced by an NADPH-dependent enoyl-[acp]reductase resulting in a pimeloyl-[acp] methyl ester.
Reacting with water through a carboxylesterase, pimeloyl-[acp] methyl ester is converted into a pimeloyl-[acp] and a methanol. The pimeloyl-acp reacts with L-alanine through an 8-amino-7-oxononanoate synthase resulting in 8-amino-7-oxononanoate which in turn reacts with S-adenosylmethionine through a 7,8-diaminonanoate transaminase resulting in an S-adenosyl-4-methylthio-2-oxobutanoate and 7,8-diaminononanoate. The latter compound is then dephosphorylated through a dethiobiotin synthetase resulting in a dethiobiotin. This compound interacts with a sulfurated[sulfur carrier), a hydrogen ion, and an S-adenosylmethionine through a biotin synthase to produce biotin and releasing L-methionine and a 5-deoxyadenosine. Finally, biotin is then metabolized by a bifunctional protein resulting in pyrophosphate and biotinyl-5-AMP which in turn reacts with the same protein (bifunctional protein birA resulting in a biotin carboxyl carrying protein. This product then enters fatty acid biosynthesis.
References
Biotin Metabolism References
Howard PK, Shaw J, Otsuka AJ: Nucleotide sequence of the birA gene encoding the biotin operon repressor and biotin holoenzyme synthetase functions of Escherichia coli. Gene. 1985;35(3):321-31. doi: 10.1016/0378-1119(85)90011-3.
Pubmed: 3899863
Buoncristiani MR, Howard PK, Otsuka AJ: DNA-binding and enzymatic domains of the bifunctional biotin operon repressor (BirA) of Escherichia coli. Gene. 1986;44(2-3):255-61. doi: 10.1016/0378-1119(86)90189-7.
Pubmed: 3536662
Blattner FR, Burland V, Plunkett G 3rd, Sofia HJ, Daniels DL: Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes. Nucleic Acids Res. 1993 Nov 25;21(23):5408-17. doi: 10.1093/nar/21.23.5408.
Pubmed: 8265357
Otsuka AJ, Buoncristiani MR, Howard PK, Flamm J, Johnson C, Yamamoto R, Uchida K, Cook C, Ruppert J, Matsuzaki J: The Escherichia coli biotin biosynthetic enzyme sequences predicted from the nucleotide sequence of the bio operon. J Biol Chem. 1988 Dec 25;263(36):19577-85.
Pubmed: 3058702
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. doi: 10.1038/msb4100049. Epub 2006 Feb 21.
Pubmed: 16738553
Kauppinen S, Siggaard-Andersen M, von Wettstein-Knowles P: beta-Ketoacyl-ACP synthase I of Escherichia coli: nucleotide sequence of the fabB gene and identification of the cerulenin binding residue. Carlsberg Res Commun. 1988;53(6):357-70.
Pubmed: 3076376
Yamamoto Y, Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kimura S, Kitagawa M, Makino K, Miki T, Mitsuhashi N, Mizobuchi K, Mori H, Nakade S, Nakamura Y, Nashimoto H, Oshima T, Oyama S, Saito N, Sampei G, Satoh Y, Sivasundaram S, Tagami H, Horiuchi T, et al.: Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features. DNA Res. 1997 Apr 28;4(2):91-113. doi: 10.1093/dnares/4.2.91.
Pubmed: 9205837
Lai CY, Cronan JE: Isolation and characterization of beta-ketoacyl-acyl carrier protein reductase (fabG) mutants of Escherichia coli and Salmonella enterica serovar Typhimurium. J Bacteriol. 2004 Mar;186(6):1869-78. doi: 10.1128/jb.186.6.1869-1878.2004.
Pubmed: 14996818
Rawlings M, Cronan JE Jr: The gene encoding Escherichia coli acyl carrier protein lies within a cluster of fatty acid biosynthetic genes. J Biol Chem. 1992 Mar 25;267(9):5751-4.
Pubmed: 1556094
Oshima T, Aiba H, Baba T, Fujita K, Hayashi K, Honjo A, Ikemoto K, Inada T, Itoh T, Kajihara M, Kanai K, Kashimoto K, Kimura S, Kitagawa M, Makino K, Masuda S, Miki T, Mizobuchi K, Mori H, Motomura K, Nakamura Y, Nashimoto H, Nishio Y, Saito N, Horiuchi T, et al.: A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map. DNA Res. 1996 Jun 30;3(3):137-55. doi: 10.1093/dnares/3.3.137.
Pubmed: 8905232
Coleman J, Raetz CR: First committed step of lipid A biosynthesis in Escherichia coli: sequence of the lpxA gene. J Bacteriol. 1988 Mar;170(3):1268-74. doi: 10.1128/jb.170.3.1268-1274.1988.
Pubmed: 3277952
Heath RJ, Rock CO: Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J Biol Chem. 1995 Nov 3;270(44):26538-42. doi: 10.1074/jbc.270.44.26538.
Pubmed: 7592873
Bergler H, Hogenauer G, Turnowsky F: Sequences of the envM gene and of two mutated alleles in Escherichia coli. J Gen Microbiol. 1992 Oct;138(10):2093-100. doi: 10.1099/00221287-138-10-2093.
Pubmed: 1364817
Kater MM, Koningstein GM, Nijkamp HJ, Stuitje AR: The use of a hybrid genetic system to study the functional relationship between prokaryotic and plant multi-enzyme fatty acid synthetase complexes. Plant Mol Biol. 1994 Aug;25(5):771-90. doi: 10.1007/bf00028873.
Pubmed: 8075395
Magnuson K, Carey MR, Cronan JE Jr: The putative fabJ gene of Escherichia coli fatty acid synthesis is the fabF gene. J Bacteriol. 1995 Jun;177(12):3593-5. doi: 10.1128/jb.177.12.3593-3595.1995.
Pubmed: 7768872
Jackowski S, Rock CO: Altered molecular form of acyl carrier protein associated with beta-ketoacyl-acyl carrier protein synthase II (fabF) mutants. J Bacteriol. 1987 Apr;169(4):1469-73. doi: 10.1128/jb.169.4.1469-1473.1987.
Pubmed: 3549687
Edwards P, Nelsen JS, Metz JG, Dehesh K: Cloning of the fabF gene in an expression vector and in vitro characterization of recombinant fabF and fabB encoded enzymes from Escherichia coli. FEBS Lett. 1997 Jan 27;402(1):62-6. doi: 10.1016/s0014-5793(96)01437-8.
Pubmed: 9013860
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000785
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