Biotin and Lipoic Acid: Synthesis, Attachment, and Regulation

Cronan, John E.

doi:10.1128/ecosal.3.6.3.5

Cited by 15 publications

(27 citation statements)

References 62 publications

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“…Since the initial demonstration, purification and synthesis of lipoic acid in the early 1940s (Reed, ), much has been learned about the synthesis of this essential respiratory co‐factor in prokaryotes (Cronan et al ., ; Cronan, ). In Escherichia coli , lipoate is assembled on the lipoyl domains (LDs) of the lipoate‐dependent enzyme systems from the eight‐carbon fatty acid, octanoate, in two steps.…”

Section: Introductionmentioning

confidence: 99%

The role of the Saccharomyces cerevisiae lipoate protein ligase homologue, Lip3, in lipoic acid synthesis

Hermes

Cronan

2013

Yeast

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The covalent attachment of lipoate to the lipoyl domains (LDs) of the central metabolism enzymes pyruvate dehydrogenase (PDH) and oxoglutarate dehydrogenase (OGDH) is essential for their activation and thus for respiratory growth in Saccharomyces cerevisiae. A third lipoate-dependent enzyme system, the glycine cleavage system (GCV), is required for utilization of glycine as a nitrogen source. Lipoate is synthesized by extraction of it precursor, octanoyl-acyl carrier protein (ACP) from the pool of fatty acid biosynthetic intermediates. Alternatively, lipoate is salvaged from previously modified proteins or from growth media by lipoate protein ligases (Lpls). The first Lpl to be characterized, LplA of Escherichia coli, catalyzes two partial reactions: activation of the acyl chain by formation of acyl-AMP, followed by transfer of the acyl chain to LDs. There is a surprising diversity within the Lpl family of enzymes, several of which catalyze reactions other than ligation reactions. For example, the Bacillus subtils Lpl homologue LipM is an octanoyltransferase that transfers the octanoyl moiety from octanoyl-ACP to GCV. Another B. subtils Lpl homologue, LipL, transfers octanoate from octanoyl-GCV to other LDs in an amidotransfer reaction. Study of eukaryotic Lpls has lagged behind studies of the bacterial enzymes. We report that the Lip3 Lpl homologue of the yeast S. cerevisiae has octanoyl-CoA: protein transferase activity and discuss implications of this activity on the physiological role of Lip3 in lipoate synthesis.

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Section: Introductionmentioning

confidence: 99%

The role of the Saccharomyces cerevisiae lipoate protein ligase homologue, Lip3, in lipoic acid synthesis

Hermes

Cronan

2013

Yeast

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“…1A). Hence, lipoic acid is an atypical enzyme cofactor in that it is assembled on its cognate proteins rather than being wholly assembled before its covalent attachment, as is the case with biotin, another covalently attached coenzyme (5).…”

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confidence: 99%

Development and retention of a primordial moonlighting pathway of protein modification in the absence of selection presents a puzzle

Cao

Hong

Zhu

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Lipoic acid is synthesized by a remarkably atypical pathway in which the cofactor is assembled on its cognate proteins. An octanoyl moiety diverted from fatty acid synthesis is covalently attached to the acceptor protein, and sulfur insertion at carbons 6 and 8 of the octanoyl moiety form the lipoyl cofactor. Covalent attachment of this cofactor is required for function of several central metabolism enzymes, including the glycine cleavage H protein (GcvH). In , GcvH is the sole substrate for lipoate assembly. Hence lipoic acid-requiring 2-oxoacid dehydrogenase (OADH) proteins acquire the cofactor only by transfer from lipoylated GcvH. Lipoyl transfer has been argued to be the primordial pathway of OADH lipoylation. The pathway where lipoate is directly assembled on both its GcvH and OADH proteins, is proposed to have arisen later. Because roughly 3 billion years separate the divergence of these bacteria, it is surprising that GcvH functionally substitutes for the protein in lipoyl transfer. Known and putative GcvHs from other bacteria and eukaryotes also substitute for GcvH in OADH modification. Because glycine cleavage is the primary GcvH role in ancestral bacteria that lack OADH enzymes, lipoyl transfer is a "moonlighting" function: that is, development of a new function while retaining the original function. This moonlighting has been conserved in the absence of selection by some, but not all, GcvH proteins. Moreover, encodes five putative GcvHs, two of which have the moonlighting function, whereas others function only in glycine cleavage.

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“…The extensive genetic analysis of the E. coli biotin biosynthetic pathway gave only two candidates as possible pimeloyl moiety synthetic genes, bioC and bioH [8]. These genes had been placed early in the pathway because the biotin requirement of bioC and bioH mutant stains was satisfied by each of the intermediates that accumulated in the culture media of mutant strains blocked in known steps of the pathway.…”

Section: The Bioc-bioh Pathway Of Pimelate Synthesismentioning

confidence: 99%

“…In this hypothesis [8] BioC would convert the free carboxyl group of a malonyl thioester (probably malonyl-CoA) to its methyl ester (Fig. 2).…”

Section: The Bioc-bioh Pathway Of Pimelate Synthesismentioning

confidence: 99%

“…DTB was assayed rather than biotin to avoid BioB, a notoriously unstable S -adenosyl methionine radical enzyme that inserts the biotin sulfur atom [8]. Dialyzed cell free extracts of wild type E. coli strains synthesized DTB when the extracts were supplemented with the precursors required for fatty acid and DTB synthesis ( de novo fatty acid synthesis in such extracts was demonstrated many years ago, but this seems the first example of in vitro coupling of the biotin synthetic enzymes).…”

Section: The Bioc-bioh Pathway Of Pimelate Synthesismentioning

confidence: 99%

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Synthesis of the α,ω-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway

Cronan

Lin

2011

Current Opinion in Chemical Biology

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Biotin synthesis requires the C7 α, ω-dicarboxylic acid, pimelic acid. Although pimelic acid was known to be primarily synthesized by a head to tail incorporation of acetate units, the synthetic mechanism was unknown. It has recently been demonstrated that in most bacteria the biotin pimelate moiety is synthesized by a modified fatty acid synthetic pathway in which the biotin synthetic intermediates are O-methyl esters disguised to resemble the canonical intermediates of the fatty acid synthetic pathway. Upon completion of the pimelate moiety, the methyl ester is cleaved. A very restricted set of bacteria have a different pathway in which the pimelate moiety is formed by cleavage of fatty acid synthetic intermediates by BioI, a member of the cytochrome P450 family.

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Biotin and Lipoic Acid: Synthesis, Attachment, and Regulation

Cited by 15 publications

References 62 publications

The role of the Saccharomyces cerevisiae lipoate protein ligase homologue, Lip3, in lipoic acid synthesis

The role of the Saccharomyces cerevisiae lipoate protein ligase homologue, Lip3, in lipoic acid synthesis

Development and retention of a primordial moonlighting pathway of protein modification in the absence of selection presents a puzzle

Synthesis of the α,ω-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway

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