Butyryl-CoA:acetoacetate CoA-transferase from a lysine-fermenting Clostridium

Barker, H. A.; Jeng, Ingming; Neff, Norton H.; Robertson, John M.; Tam, F K; Hosaka, Shigetoshi

doi:10.1016/s0021-9258(17)38133-4

Cited by 39 publications

(5 citation statements)

References 26 publications

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“…Both COA-PWY and PANTOSYN-PWY synthesize CoA, and OANTIGEN-PWY contains a catalysis step by acetyl-CoA and reduces CoA. Due to the competitive relationship, CoA inhibits the enzymatic reactions of the acetoacetyl-CoA transferase, which produces acetate [ 29 , 30 ], while the HC-enriched pathway PWY-6435 converts CoA to acetyl-CoA.…”

Section: Resultsmentioning

confidence: 99%

Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis

Liu

Jiang

et al. 2021

BMC Med

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Background Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients. Methods Our study recruited 53 pediatric MG patients and 46 age- and gender-matched healthy controls (HC). We sequenced the fecal samples of recruited individuals using whole-genome shotgun sequencing and analyzed the data with in-house bioinformatics pipeline. Results We built an MG disease classifier based on the abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale. The classifier obtained 94% area under the curve (AUC) in cross-validation and 84% AUC in the independent validation cohort. Gut microbiome analysis revealed the presence of human adenovirus F/D in 10 MG patients. Significantly different pathways and gene families between MG patients and HC belonged to P. copri, Clostridium bartlettii, and Bacteroides massiliensis. Based on functional annotation, we found that the gut microbiome affects the production of short-chain fatty acids (SCFAs), and we confirmed the decrease in SCFA levels in pediatric MG patients via serum tests. Conclusions The study indicated that altered fecal microbiota might play vital roles in pediatric MG’s pathogenesis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric MG.

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Section: Resultsmentioning

confidence: 99%

Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis

Liu

Jiang

et al. 2021

BMC Med

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“…GCT catalyzes the transfer of the CoA moiety from acetyl CoA to (R)-2hydroxyglutarate and related compounds like glutaconate, from which the name of the enzyme derives. As the 'energy-rich' thiol ester bond is conserved in this reaction, this mode of carboxylate activation is preferred by anaerobic fermentative bacteria which have to cope with low ATP yields [2,[4][5][6][7][8][9][10][11]. CoA-transferases are also found in aerobic bacteria [12] (MS Shanley, A Harrison and LN Ornston, (1991) GenBank entries: pir A44570 and B44570) and in the related mitochondria of man and animals.…”

Section: Introductionmentioning

confidence: 99%

Glutaconate CoA-transferase from Acidaminococcus fermentans: the crystal structure reveals homology with other CoA-transferases

Mack²,

et al. 1997

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The active site of GCT is located at the interface of subunits A and B and is formed by loops of both subunits. The funnel-shaped opening to the active site has a depth and diameter of about 20 A with the catalytic residue, Glu54 of subunit B, at the bottom. The active-site glutamate residue is stabilized by hydrogen bonds. Despite very low amino acid sequence similarity, subunits A and B reveal a similar overall fold. Large parts of their structures can be spatially superimposed, suggesting that both subunits have evolved from a common ancestor.

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“…The concentrations of CoASH, acetyl-CoA, and glutaconyl-CoA, or any other CoA-ester substrate of the transferase were determined with 5 μg CoA-transferase in a single assay. 30 Malate dehydrogenase, 35 crotonase 36 and fumarase 37 were assayed by described procedures.…”

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confidence: 99%

Substrate Specificity of 2-Hydroxyglutaryl-CoA Dehydratase from Clostridium symbiosum: Toward a Bio-Based Production of Adipic Acid

et al. 2011

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Expression of six genes from two glutamate fermenting clostridia converted Escherichia coli into a producer of glutaconate from 2-oxoglutarate of the general metabolism (Djurdjevic, I. et al. 2010, Appl. Environ. Microbiol.77, 320-322). The present work examines whether this pathway can also be used to reduce 2-oxoadipate to (R)-2-hydroxyadipic acid and dehydrate its CoA thioester to 2-hexenedioic acid, an unsaturated precursor of the biotechnologically valuable adipic acid (hexanedioic acid). 2-Hydroxyglutaryl-CoA dehydratase from Clostridium symbiosum, the key enzyme of this pathway and a potential radical enzyme, catalyzes the reversible dehydration of (R)-2-hydroxyglutaryl-CoA to (E)-glutaconyl-CoA. Using a spectrophotometric assay and mass spectrometry, it was found that (R)-2-hydroxyadipoyl-CoA, oxalocrotonyl-CoA, muconyl-CoA, and butynedioyl-CoA, but not 3-methylglutaconyl-CoA, served as alternative substrates. Hydration of butynedioyl-CoA most likely led to 2-oxosuccinyl-CoA, which spontaneously hydrolyzed to oxaloacetate and CoASH. The dehydratase is not specific for the CoA-moiety because (R)-2-hydroxyglutaryl-thioesters of N-acetylcysteamine and pantetheine served as almost equal substrates. Whereas the related 2-hydroxyisocaproyl-CoA dehydratase generated the stable and inhibitory 2,4-pentadienoyl-CoA radical, the analogous allylic ketyl radical could not be detected with muconyl-CoA and 2-hydroxyglutaryl-CoA dehydratase. With the exception of (R)-2-hydroxyglutaryl-CoA, all mono-CoA-thioesters of dicarboxylates used in this study were synthesized with glutaconate CoA-transferase from Acidaminococcus fermentans. The now possible conversion of (R)-2-hydroxyadipate via (R)-2-hydroxyadipoyl-CoA and 2-hexenedioyl-CoA to 2-hexenedioate paves the road for a bio-based production of adipic acid.

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Butyryl-CoA:acetoacetate CoA-transferase from a lysine-fermenting Clostridium

Cited by 39 publications

References 26 publications

Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis

Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis

Glutaconate CoA-transferase from Acidaminococcus fermentans: the crystal structure reveals homology with other CoA-transferases

Substrate Specificity of 2-Hydroxyglutaryl-CoA Dehydratase from Clostridium symbiosum: Toward a Bio-Based Production of Adipic Acid

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