Biology subjects

Appel, L.

Publications and source records attributed to Appel, L..

3 recordsLinked to original sources

bioRxiv2026

Powering methanogenesis from fatty acids by a twin-heme-mediated reverse redox-loop

The conversion of organic matter into methane is central to the global carbon cycle and engineered biogas production. In this process, syntrophic bacteria oxidize fatty acid fermentation products to acetate, coupled to the generation of H2 or formate, which are subsequently utilized by methanogenic archaea. During fatty acid {beta}-oxidation, a membrane-bound electron-transferring flavoprotein (ETF):methylmenaquinone (MMK) oxidoreductase complex (EMO) has been proposed to drive endergonic electron transfer from reduced ETF to CO2 through a reverse redox loop, with its mechanistic basis remaining unresolved. Here we report cryo-electron microscopy structures of EMO and the EMO-ETF complex from Syntrophus aciditrophicus at 2.0 and 3.0 [A] resolution, respectively. Complex formation induces substantial conformational rearrangements in ETF, positioning its flavin for efficient electron transfer to non-cubane [4Fe:4S] and [4Fe:5S] clusters. The membrane-integral domain harbors three heme b cofactors, including a specialized twin-heme unit that mediates proton-motive-force-driven MMK reduction. The structural and functional similarity of EMOs to heterodisulfide reductases, together with their broad distribution across bacteria and archaea, suggests an evolutionary link between methanogenesis and fatty acid {beta}-oxidation, illustrating how ancient redox systems were repurposed for new metabolic functions.

microbiology↗

bioRxiv2026

Coupling of electron-bifurcation modules powers aromatic ring reduction beyond the biological redox window

Microbial degradation of ubiquitous aromatic compounds is central to the global carbon cycle and bioremediation, yet the intrinsic stability of aromatic rings poses a major barrier to their breakdown. Under strictly anaerobic conditions, class II benzoyl-CoA reductases (BCRII) catalyse the key step of this process, a Birch-like reduction of the aromatic ring to a cyclic diene at a tungsten cofactor. This reaction operates beyond the redox limits of conventional biological electron transfer, yet the mechanism by which BCRII generates such extreme reducing power has remained unclear. Here, high-resolution cryo-electron microscopy, in situ cryo-electron tomography, and enzymatic analyses reveal that the one-MDa BCRII complex from Geobacter metallireducens links two distinct flavin-based electron-bifurcation modules, previously characterised in hydrogenases and heterodisulfide reductases, to drive aromatic ring reduction. Reduced ferredoxin and NADH deliver electrons through sequential confurcation and bifurcation to the catalytic site, while cryo-electron tomography of native cells identifies electron-transferring flavoprotein as the second acceptor directing high-potential electrons into the respiratory chain. These results show that modular FBEB units can be hierarchically assembled to extend metabolic redox capacity, highlighting their versatility as adaptable components for electron transfer pathways.

biochemistry↗

bioRxiv2017

Differential Impacts of Dietary Modification on Individual Metabolic Phenotypes and their Relationship to Blood Pressure: Evidence of Latent Dietary Responder Sub-phenotypes

BackgroundHypertension is a worldwide public health issue with significant comorbidity and mortality. We aimed to identify urinary metabolic phenotypes associated with three healthy diets and to establish their relationship to blood pressure (BP).\n\nMethods and Results--24-h urine samples from 158 participants, with pre-hypertension and hypertension, consumed a carbohydrate-rich, a protein-rich and a monounsaturated fat-rich healthy diet (6-week per diet) in randomized order, were analyzed by nuclear magnetic resonance spectroscopy. Combinations of metabolites significantly associated with each diet were identified, and associations between these metabolites and cardiovascular disease risk were established. We found coherent responses to all three diets including increased excretion of metabolites originating from vegetables/fruits, protein, tryptophan metabolism and gut microbial-mammalian co-metabolism. Proline betaine (marker of citrus fruit) was significantly inversely associated with systolic BP; 4-cresyl sulfate (gut microbial metabolite) inversely correlated with both systolic and diastolic BP; and hippurate (gut microbial metabolite) - directly associated with reduced systolic BP.\n\nConclusionsVariation in metabolic phenotypes in response to specific diets may hold clues as to the mechanisms underlying inter-individual differences in dietary response. Stratification of individuals based on diet-specific urinary phenotypes highlights the feasibility for individualized approaches to dietary therapy for lowering BP.\n\nClinical Trial RegistrationThis intervention study is registered at http://www.clinicaltrials.gov as NCT00051350

molecular biology↗