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MetaCyc Pathway: lipoate biosynthesis and incorporation III (Bacillus)

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Lipoate Biosynthesis

Some taxa known to possess this pathway include ? : Bacillus subtilis , Bacillus subtilis subtilis 168

Expected Taxonomic Range: Bacteria

Summary:
General Background

Lipoate is an organosulfur compound that contains a ditholane ring, which is a cyclic disulfide. Lipoate is used as an essential cofactor by many enzyme complexes involved in oxidative metabolism, including the pyruvate dehydrogenase complex [Herbert75, Stepp81, Reed93], the 2-oxoglutarate decarboxylation to succinyl-CoA [Herbert75, Stepp81, Reed93], the 2-oxoisovalerate decarboxylation to isobutanoyl-CoA [Reed90], and the glycine cleavage [Vanden91, Reed93].

Each of these enzyme complexes is composed of multiple copies of three enzymes: a substrate-specific decarboxylase-dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2) specific for each type of complex, and a dihydrolipoamide dehydrogenase (E3). The (E2) proteins have a dedicated lipoyl domain. In order for the complex to be active, lipoate must be attached to the lipoyl domain by an amide linkage between its carboxylate moiety and a specific lysine residue in the enzyme [Reed93]..

E1 catalyzes a reaction in which the substrate is attached to the lipoate cofactor and decarboxylated. During this reaction, the lipoate cofactor is reduced to dihydriolipoate. E2 then catalyzes an acyl transfer step, in which the product of the reaction is released. Finally, E3 catalyzes the oxidation of the dihydrolipoyl cofactor back to lipoyl form, with NAD being the ultimate electron acceptor [Reed90].

About This Pathway

The biosynthesis of lipoate is unusual, and shares the same mechanism as the biosynthesis of biotin. The precursor octanoate molecule is first attached to a specific L-lysine residue within the lipoyl domain, and is then converted to lipoate.

In Escherichia coli the pathway consists of two steps - first enzyme in the pathway, encoded by either lplA or lipB, transfers either free octanoate or the octanoate moiety from octanoate-[acp] molecue, respectively, to a specific lysyl residue in any of the lipoate-dependent enzymes, while another enzyme, encoded by lipA, converts the bound octanoate to lipoate (see lipoate biosynthesis and incorporation I and lipoate biosynthesis and incorporation II).

In Bacillus subtilis the pathway is somewhat mnore complex. The first enzyme, encoded by lipM, can transfer the octanoate from octanoyl-[acp] only to the H protein of the glycine cleavage system. Thus, a second enzyme, an amidotransferase encoded by lipL, is required to complete the transfer of the octanoate moiety from the octanoylated GcvH protein to the E2 components of the 2-oxo acid dehydrogenases, where it is converted to lipoate by a LipA enzyme [Christensen11a].

Variants: lipoate biosynthesis and incorporation (glycine cleavage system, yeast) , lipoate biosynthesis and incorporation (pyruvate dehydrogenase and oxoglutarate dehydrogenase, yeast) , lipoate biosynthesis and incorporation I , lipoate biosynthesis and incorporation II , lipoate salvage I , lipoate salvage II

Credits:
Created 01-Feb-2012 by Caspi R , SRI International


References

Christensen11a: Christensen QH, Martin N, Mansilla MC, de Mendoza D, Cronan JE (2011). "A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis." Mol Microbiol 80(2);350-63. PMID: 21338421

Herbert75: Herbert AA, Guest JR (1975). "Lipoic acid content of Escherichia coli and other microorganisms." Arch Microbiol 106(3);259-66. PMID: 814874

Reed90: Reed LJ, Hackert ML (1990). "Structure-function relationships in dihydrolipoamide acyltransferases." J Biol Chem 265(16);8971-4. PMID: 2188967

Reed93: Reed KE, Cronan JE (1993). "Lipoic acid metabolism in Escherichia coli: sequencing and functional characterization of the lipA and lipB genes." J Bacteriol 175(5);1325-36. PMID: 8444795

Stepp81: Stepp LR, Bleile DM, McRorie DK, Pettit FH, Reed LJ (1981). "Use of trypsin and lipoamidase to study the role of lipoic acid moieties in the pyruvate and alpha-ketoglutarate dehydrogenase complexes of Escherichia coli." Biochemistry 20(16);4555-60. PMID: 6794598

Vanden91: Vanden Boom TJ, Reed KE, Cronan JE (1991). "Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system." J Bacteriol 173(20);6411-20. PMID: 1655709

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Byers07: Byers DM, Gong H (2007). "Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family." Biochem Cell Biol 85(6);649-62. PMID: 18059524

Christensen10: Christensen QH, Cronan JE (2010). "Lipoic Acid Synthesis: A New Family of Octanoyltransferases Generally Annotated as Lipoate Protein Ligases." Biochemistry. PMID: 20882995

Frey01: Frey PA (2001). "Radical mechanisms of enzymatic catalysis." Annu Rev Biochem 70;121-48. PMID: 11395404

GOA00: GOA (2000). "Gene Ontology annotation based on Swiss-Prot keyword mapping."

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA07: GOA, UniProt (2007). "Gene Ontology annotation based on Swiss-Prot Subcellular Location vocabulary mapping."

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Martin09a: Martin N, Lombardia E, Altabe SG, de Mendoza D, Mansilla MC (2009). "A lipA (yutB) mutant, encoding lipoic acid synthase, provides insight into the interplay between branched-chain and unsaturated fatty acid biosynthesis in Bacillus subtilis." J Bacteriol 191(24);7447-55. PMID: 19820084

Martin11b: Martin N, Christensen QH, Mansilla MC, Cronan JE, de Mendoza D (2011). "A novel two-gene requirement for the octanoyltransfer reaction of Bacillus subtilis lipoic acid biosynthesis." Mol Microbiol 80(2);335-49. PMID: 21338420

Miller00: Miller JR, Busby RW, Jordan SW, Cheek J, Henshaw TF, Ashley GW, Broderick JB, Cronan JE, Marletta MA (2000). "Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein." Biochemistry 39(49);15166-78. PMID: 11106496

Smaczynskade04: Smaczynska-de Rooij I, Migdalski A, Rytka J (2004). "Alpha-Ketoglutarate dehydrogenase and lipoic acid synthase are important for the functioning of peroxisomes of Saccharomyces cerevisiae." Cell Mol Biol Lett 9(2);271-86. PMID: 15213808

Sulo93: Sulo P, Martin NC (1993). "Isolation and characterization of LIP5. A lipoate biosynthetic locus of Saccharomyces cerevisiae." J Biol Chem 268(23);17634-9. PMID: 8349643


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Nov 22, 2014, BIOCYC13B.