Studies in the metabolism of the strict anaerobes (genus <i>Clostridium</i>)

Stickland, L. H.

doi:10.1042/bj0281746

Cited by 245 publications

(73 citation statements)

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“…The process, which is now known after his name as the Stickland reaction, involves the transfer of reducing equivalents from one amino acid to another coupled to the formation of ATP. The overall process occurs in several stages, as shown in Scheme 1, and may be regarded to involve initially a two-step oxidation [Eqns (1) and (2)] of one of the amino acids, for example alanine, to produce two equivalents of a reduced coenzyme, presumably NAD(P)H. In vivo the latter then, through a complex electron transport system, participates in the reductive deamination of the second amino acid [Eqn (3)].…”

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confidence: 99%

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Barnard

Akhtar

1979

European Journal of Biochemistry

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Clostridial glycine reductase multienzyme complex which catalyses the reaction :Glycine + ADP + Pi + 2H -+ Acetate + ATP + NH3 was solubilised and fractionated essentially according to the method of Stadtman [T. C. Stadtman (1970) Methods Enzymol. I7A, 956 -9661 into two components : protein A and 'glycine reductase' fraction. A reconstituted system obtained by combining the two components in the presence of dithiothreitol catalysed the conversion of glycine into acetate concomitant with the phosphorylation of ADP to ATP. Using the reconstitued system, in which the unwanted enzymic activity catalyzing an exchange of the ct hydrogen atoms of glycine with the protons of the medium had been greatly reduced, it was found that the conversion of (2RS)-[2-14C, 2-3H1]glycine (3H/'4C = 7.16) into acetate (3H/14C = 7.03) was attended by the retention of both the C-2 hydrogen atoms of glycine. Conversion of (2S)-[2-2H1, 2-3Hl]glycine and (2R)-[2-2H1, 2-3Hl]glycine by the reconstituted system gave (2S)-acetate and (2R)-acetate respectively showing that the reductive deamination of glycine occurs through an inversion of configuration. The cumulative information available on the glycine reductase reaction is embodied in a hypothetical mechanism of action for the enzyme.

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confidence: 99%

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Barnard

Akhtar

1979

European Journal of Biochemistry

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“…13 These organisms carry out Stickland fermentation wherein pairs of amino acids are used as electron donors and acceptors in energy metabolism. 12 It was known as early as 1934 that Pro and Hyp can be used as electron acceptors in such fermentations. 12 Furthermore, it was shown that Hyp can induce the expression of an enzyme responsible for Pro reduction in C. difficile .…”

Section: Introductionmentioning

confidence: 99%

“…12 It was known as early as 1934 that Pro and Hyp can be used as electron acceptors in such fermentations. 12 Furthermore, it was shown that Hyp can induce the expression of an enzyme responsible for Pro reduction in C. difficile . 13 In contrast to the characterized pathway for Pro reduction (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…2A), the enzymes and downstream metabolites involved in Hyp fermentation had not been identified until our work. 12

10.1080/19490976.2018.1435244-F0002Figure 2.Characterized pathways for Hyp metabolism. (A) Pathway for Stickland fermentation using l -proline (Pro) as an electron acceptor.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, HypD is present in species previously demonstrated to use Hyp and Pro as electron acceptors ( C. difficile, Clostridium sporogenes ). 12 , 13 Notably, ∼65% of the Clostridiales species that possess the prd operon, which is essential for Pro reduction, also encode HypD. 13 , 14 In these species, the conserved proC gene (encoding P5CR) adjacent to hypD provides a strong indication that Hyp is metabolized to Pro and used as an electron acceptor.…”

Section: Introductionmentioning

confidence: 99%

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Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity

2018

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The discovery of enzymes responsible for previously unappreciated microbial metabolic pathways furthers our understanding of host-microbe and microbe-microbe interactions. We recently identified and characterized a new gut microbial glycyl radical enzyme (GRE) responsible for anaerobic metabolism of trans-4-hydroxy-l-proline (Hyp). Hyp dehydratase (HypD) catalyzes the removal of water from Hyp to generate Δ1-pyrroline-5-carboxylate (P5C). This enzyme is encoded in the genomes of a diverse set of gut anaerobes and is prevalent and abundant in healthy human stool metagenomes. Here, we discuss the roles HypD may play in different microbial metabolic pathways as well as the potential implications of this activity for colonization resistance and pathogenesis within the human gut. Finally, we present evidence of anaerobic Hyp metabolism in sediments through enrichment culturing of Hyp-degrading bacteria, highlighting the wide distribution of this pathway in anoxic environments beyond the human gut.

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Clostridioides difficile 630Δerm in silico and in vivo – quantitative growth and extensive polysaccharide secretion

et al. 2017

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Antibiotic‐associated infections with Clostridioides difficile are a severe and often lethal risk for hospitalized patients, and can also affect populations without these classical risk factors. For a rational design of therapeutical concepts, a better knowledge of the metabolism of the pathogen is crucial. Metabolic modeling can provide a simulation of quantitative growth and usage of metabolic pathways, leading to a deeper understanding of the organism. Here, we present an elaborate genome‐scale metabolic model of C. difficile 630Δerm. The model iHD992 includes experimentally determined product and substrate uptake rates and is able to simulate the energy metabolism and quantitative growth of C. difficile. Dynamic flux balance analysis was used for time‐resolved simulations of the quantitative growth in two different media. The model predicts oxidative Stickland reactions and glucose degradation as main sources of energy, while the resulting reduction potential is mostly used for acetogenesis via the Wood–Ljungdahl pathway. Initial modeling experiments did not reproduce the observed growth behavior before the production of large quantities of a previously unknown polysaccharide was detected. Combined genome analysis and laboratory experiments indicated that the polysaccharide is an acetylated glucose polymer. Time‐resolved simulations showed that polysaccharide secretion was coupled to growth even during unstable glucose uptake in minimal medium. This is accomplished by metabolic shifts between active glycolysis and gluconeogenesis which were also observed in laboratory experiments.

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Studies in the metabolism of the strict anaerobes (genus Clostridium)

Cited by 245 publications

References 3 publications

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity

Clostridioides difficile 630Δerm in silico and in vivo – quantitative growth and extensive polysaccharide secretion

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