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Pathway Description
Pantothenate and CoA Biosynthesis
Escherichia coli str. K-12 substr. DH10B
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2024-11-12
Last Updated: 2024-11-13
The CoA biosynthesis requires compounds from two other pathways: aspartate metabolism and valine biosynthesis. It requires a Beta-Alanine and R-pantoate. The compound (R)-pantoate is generated in two reactions, as shown by the interaction of alpha-ketoisovaleric acid, 5,10 methylene-THF and water through a 3-methyl-2-oxobutanoate hydroxymethyltransferase resulting in a tetrahydrofolic acid and a 2-dehydropantoate. 2-dehydropantoate interacts with hydrogen through a NADPH driven acetohydroxy acid isomeroreductase resulting in the release of NADP and R-pantoate. On the other hand L-aspartic acid interacts with a hydrogen ion and gets decarboxylated through an Aspartate 1- decarboxylase resulting in a carbon dioxide and a Beta-alanine. Beta-alanine and R-pantoate interact with an ATP driven pantothenate synthetase resulting in pyrophosphate, AMP, hydrogen ion and pantothenic acid. Pantothenic acid is phosphorylated through a ATP-driven pantothenate kinase resulting in a ADP, a hydrogen ion and D-4'-Phosphopantothenate. The latter interacts with a CTP and a L-cysteine resulting in a fused 4'phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a hydrogen ion, a pyrophosphate, a CMP and 4-phosphopantothenoylcysteine. The latter compound interacts with a hydrogen ion through a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in the release of carbon dioxide and 4-phosphopantetheine. 4-phosphopantetheine reacts with ATP, hydrogen ion and an phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA. Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in a ADP , a hydrogen ion and a Coenzyme A. Dephospho-CoA also reacts with 2-(5''-triphosphoribosyl)-3'-dephosphocoenzyme-A synthase (citG) to form both adenine and 2'-(5-Triphosphoribosyl)-3'-dephospho-CoA. In this pathway, all enzymes are essential for the cell growth. Biosynthetic pathway for producing CoA is same for most organisms (with exception of differences in the functionality of involved enzymes). In plants, every step is catalyzed by monofunctional enzymes instead of biofunctional enzymes.
References
Pantothenate and CoA Biosynthesis References
Jones CE, Brook JM, Buck D, Abell C, Smith AG: Cloning and sequencing of the Escherichia coli panB gene, which encodes ketopantoate hydroxymethyltransferase, and overexpression of the enzyme. J Bacteriol. 1993 Apr;175(7):2125-30. doi: 10.1128/jb.175.7.2125-2130.1993.
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Zheng R, Blanchard JS: Kinetic and mechanistic analysis of the E. coli panE-encoded ketopantoate reductase. Biochemistry. 2000 Apr 4;39(13):3708-17. doi: 10.1021/bi992676g.
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Merkel WK, Nichols BP: Characterization and sequence of the Escherichia coli panBCD gene cluster. FEMS Microbiol Lett. 1996 Oct 1;143(2-3):247-52. doi: 10.1016/0378-1097(96)00321-7.
Pubmed: 8837478
Song WJ, Jackowski S: Cloning, sequencing, and expression of the pantothenate kinase (coaA) gene of Escherichia coli. J Bacteriol. 1992 Oct;174(20):6411-7. doi: 10.1128/jb.174.20.6411-6417.1992.
Pubmed: 1328157
Song WJ, Jackowski S: coaA and rts are allelic and located at kilobase 3532 on the Escherichia coli physical map. J Bacteriol. 1992 Mar;174(5):1705-6. doi: 10.1128/jb.174.5.1705-1706.1992.
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Flamm JA, Friesen JD, Otsuka AJ: The nucleotide sequence of the Escherichia coli rts gene. Gene. 1988 Dec 30;74(2):555-8. doi: 10.1016/0378-1119(88)90189-8.
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Burland V, Plunkett G 3rd, Daniels DL, Blattner FR: DNA sequence and analysis of 136 kilobases of the Escherichia coli genome: organizational symmetry around the origin of replication. Genomics. 1993 Jun;16(3):551-61. doi: 10.1006/geno.1993.1230.
Pubmed: 7686882
Miller JR, Ohren J, Sarver RW, Mueller WT, de Dreu P, Case H, Thanabal V: Phosphopantetheine adenylyltransferase from Escherichia coli: investigation of the kinetic mechanism and role in regulation of coenzyme A biosynthesis. J Bacteriol. 2007 Nov;189(22):8196-205. doi: 10.1128/JB.00732-07. Epub 2007 Sep 14.
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Clementz T, Raetz CR: A gene coding for 3-deoxy-D-manno-octulosonic-acid transferase in Escherichia coli. Identification, mapping, cloning, and sequencing. J Biol Chem. 1991 May 25;266(15):9687-96.
Pubmed: 2033061
Sofia HJ, Burland V, Daniels DL, Plunkett G 3rd, Blattner FR: Analysis of the Escherichia coli genome. V. DNA sequence of the region from 76.0 to 81.5 minutes. Nucleic Acids Res. 1994 Jul 11;22(13):2576-86. doi: 10.1093/nar/22.13.2576.
Pubmed: 8041620
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 SMP0000848
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