Fumarate reductase superfamily: A diverse group of enzymes whose evolution is correlated to the establishment of different metabolic pathways

Jardim-Messeder, Douglas; Cabreira-Cagliari, Caroline; Rauber, Rafael; Turchetto‐Zolet, Andreia Carina; Margis, Rogério; Margis‐Pinheiro, Márcia

doi:10.1016/j.mito.2017.01.002

Cited by 25 publications

(21 citation statements)

References 59 publications

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“…data of a previous study led to the identification of set of genes that likely form an operon ( Figure 1), starting with the gene encoding a fumarate hydratase, the enzyme responsible for the interconversion of malate and fumarate (3). This operon further contains a gene homologous to the flavoprotein subunit of fumarate reductase/succinate dehydrogenase (FrdA), the core subunit that is shared between all known fumarate reductases and succinate dehydrogenases (6), and the only isoform of it present in P.…”

Section: Hypothesis Introductionmentioning

confidence: 99%

“…Fumarate reductasesThe various enzymes responsible for the interconversion of fumarate and succinate (i.e. fumarate reductases and succinate dehydrogenases, FRD/SDH) are diverse in their subunit configurations, but are all part of a larger protein superfamily based on a homologous flavoprotein, which also includes L-aspartate oxidases, anaerobic glycerol-3-phosphate dehydrogenases, and adenylyl-sulfate reductases(6).FRD/SDHs can be divided in two main groups: soluble and membrane-bound. The latter are part of the electron Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 22 December 2019 doi:10.20944/preprints201912.0288.v1 transport chain, and thus often linked to proton translocation, and are generally referred to as the succinate:quinone oxidoreductase superfamily (Figure 2) (9).…”

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Identification of a Novel Fumarate Reductase Potentially Involved in Electron Bifurcation

Kranenburg¹,

Koendjbiharie²

2019

Preprint

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In the succinic acid-producing bacterium Pseudoclostridium thermosuccinogenes the fumarate reductase (FRD) genes reside in an operon together with those encoding an electron bifurcating complex (FlxABCD-HdrABC) that shuttles electrons from NADH to ferredoxin and a disulfide bond. Based on phylogeny and genomic co-occurrence we propose two hypothetical mechanisms via which the FRD is involved in electron bifurcation: (I) A disulfide bond from a hitherto unknown cofactor is reduced by the electron-bifurcating FlxABCD-HdrABC complex, using NADH to generate two thiol groups, while facilitating the unfavourable reduction of ferredoxin by NADH. The disulfide bond is subsequently regenerated via the reduction of fumarate by the FRD using the previously formed thiol groups. (II) The FRD forms an integral part of the FlxABCD-HdrABC complex, and NADH is used to reduce ferredoxin and fumarate directly, without an intermediate disulfide-forming cofactor. Either way enables the conservation of additional energy by a soluble FRD, analogous to fumarate respiration.

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Section: Hypothesis Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Identification of a Novel Fumarate Reductase Potentially Involved in Electron Bifurcation

Kranenburg¹,

Koendjbiharie²

2019

Preprint

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“…The various enzymes responsible for the interconversion of fumarate and succinate (i.e. fumarate reductases and succinate dehydrogenases, FRD/SDH) are diverse in their subunit configurations, but are all part of a larger protein superfamily based on a homologous flavoprotein, which also includes l-aspartate oxidases, anaerobic glycerol-3-phosphate dehydrogenases, and adenylyl-sulfate reductases [124]. FRD/SDHs can be divided in two main groups: soluble and membrane-bound.…”

Section: Fumarate Reductasesmentioning

confidence: 99%

“…data of a previous study led to the identification of set of genes that likely form an operon (Figure 1), starting with the gene encoding a fumarate hydratase, the enzyme responsible for the interconversion of malate and fumarate [143]. This operon further contains a gene homologous to the flavoprotein subunit of fumarate reductase/succinate dehydrogenase (FrdA); the core subunit that is shared between all known fumarate reductases and succinate dehydrogenases [124]. Surprisingly, eight more genes are present in between the fumarate hydratase and the fumarate reductase flavoprotein subunit.…”

Section: Introductionmentioning

confidence: 99%

“…In the latter, CO2 is used, and one ATP equivalent is formed, whereas in the former, HCO3is used, but no ATP equivalents are formed. Moreover, the fumarate reductase reaction can be linked to different cofactors in different organisms [124], which can also have further implications (Chapter 4). In the case quinol:fumarate reductase is used, four protons can be pumped out by a Type 1 NADH dehydrogenase, allowing the generation of up to 1 ATP, per succinic acid molecule formed.…”

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The thermophilic route to succinic acid

Koendjbiharie¹

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Chapter 1-General introduction and thesis outline Biotechnology and the biobased economy Many nuanced definitions exist for biotechnology that generally describe the use of living systems, organisms, or parts thereof in order to alter or generate products, systems, or environments to benefit people. As such, biotechnology is a very broad, and broadly used term that covers a plethora of different fields and technologies, ranging from ancient beer brewing and winemaking processes to the production of modern therapeutics using engineered eukaryotic cell-lines. Agriculture itself, however, is generally not considered biotechnology, even though it would fit the definition. Since about fifteen years ago, it has become common to distinguish between different types of biotechnology using colors: white (industrial) biotechnology, red (pharmaceutical) biotechnology, green (agro) biotechnology, and blue (marine) biotechnology are the most common distinctions that are used, but many more exist and they are not always used consistently. * Sugar cane/ Maize Malic anhydride 6.8 Bio succinic acid Today 1.3-3.6 / 2.3-4.6* Future 0.9-2.1 / 1.8-2.9* [226] Chemical DSP GJ/t (NREU) Comments Malic anhydride-67.7 * Sugar cane / Maize Petr. succinic acid-96.3 Bio succinic acid Direct crystallization 44.9 / 66.5* Natural and engineered succinic acid producers A large variety of organisms have been studied for their capacity to naturally produce succinic acid, and several natural and non-natural producers-both bacteria and eukaryotes-have been engineered to produce (more) succinic acid. The most-studied species are briefly described below. Bacteria Actinobacillus succinogenes A. succinogenes is a facultative anaerobic, pleomorphic, Gram-negative rod, first isolated from bovine rumen [103]. It is capnophilic (CO2-"loving") and can grow on a broad range of pentose and hexose sugars. It naturally produces succinic acid, up to 70 g/l with yields of General introduction 1 | 21 around 0.75 g/g sugar [178,249]. Succinic acid is formed via the reductive branch of the TCA cycle, which is bifurcated, with succinic acid as one of the end-points [102]. Anaerobiospirillum succiniciproducens A. succiniproducens is an anaerobic, Gram-negative, spiral shaped bacterium. It was first isolated from a dog, but is also present in humans and can-in rare cases-be the cause of bacteraemia or other types of opportunistic infections [67,131]. Similar to A. succinogenes, A. succiniproducens is a capnophile able to grow on a large range of substrates. The available CO2 concentration strongly influences the succinic acid production [250]. Yields of around 1.4 g/g glycerol have been reported [43,160]. Corynebacterium glutamicum C. glutamicum is a facultative anaerobic, Gram-positive rod. It has a long history for industrial-scale production of a variety of amino acids [310]. It is unable to grow under oxygen deprived conditions, but retains the possibility to ferment sugars allowing a process to shift easily from a biomass formation phase and a high-density production...

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