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1. An acyl‐activating enzyme ( AAE ) 3 homolog encodes an oxalyl‐ CoA synthetase in Bradysia coprophila

   https://doi.org/10.1002/pro.70549  

   Cela, Aldona; Wang, Fayna S; Guehria, Hannah; Nakata, Paul A (May 2026, Protein Science)

   Abstract Although oxalate is common in nature, our understanding of its metabolism remains incomplete. To our knowledge, no oxalate catabolic activity has been identified in any animal from the Metazoa kingdom. In this study, we identify the first oxalate degradative activity in Metazoa. We show that theBradysia coprophilagenome contains an acyl‐activating enzyme 3 (BcAAE3) that can catalyze the conversion of oxalate to oxalyl‐CoA. Based on our results, we propose that the oxalyl‐CoA synthetase activity encoded by BcAAE3 catalyzes the first step in a CoA‐dependent pathway of oxalate degradation. In addition, our findings extend the importance of the CoA‐dependent pathway of oxalate degradation from simple microbes to complex animals. 

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2. Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans

   https://doi.org/10.1073/pnas.1608262113  

   Zhang, Xinxing; Li, Kunhua; Jones, Rachel A.; Bruner, Steven D.; Butcher, Rebecca A. (September 2016, Proceedings of the National Academy of Sciences)

   Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state. 

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3. Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle

   https://doi.org/10.1038/s41598-021-98314-z  

   Omini, Joy; Wojciechowska, Izabela; Skirycz, Aleksandra; Moriyama, Hideaki; Obata, Toshihiro (December 2021, Scientific Reports)

   Abstract Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle ‘metabolon’ which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD + and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was present together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways. 

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4. The Predominance of Ammonia-Oxidizing Archaea in an Oceanic Microbial Community Amended with Cyanobacterial Lysate

   https://doi.org/10.1128/spectrum.02405-22  

   Jia, Yufeng; Lahm, Madeline; Chen, Qi; Powers, Leanne; Gonsior, Michael; Chen, Feng (February 2023, Microbiology Spectrum)

   Weinert, Emily (Ed.)

   ABSTRACT When the oligotrophic microbial community was amended with Synechococcus -derived dissolved organic matter (SDOM) and incubated under the dark condition, archaea relative abundance was initially very low but made up more than 60% of the prokaryotic community on day 60, and remained dominant for at least 9 months. The archaeal sequences were dominated by Candidatus Nitrosopumilus , the Group I.1a Thaumarchaeota. The increase of Thaumarchaeota in the dark incubation corresponded to the period of delayed ammonium oxidation upon an initially steady increase in ammonia, supporting the remarkable competency of Thaumarchaeota in energy utilization and fixation of inorganic carbon in the ocean. IMPORTANCE Thaumarchaeota, which are ammonia-oxidizing archaea (AOA), are mainly chemolithoautotrophs that can fix inorganic carbon to produce organic matter in the dark. Their distinctive physiological traits and high abundance in the water column indicate the significant ecological roles they play in the open ocean. In our study, we found predominant Thaumarchaeota in the microbial community amended with cyanobacteria-derived lysate under the dark condition. Furthermore, Thaumarchaeota remained dominant in the microbial community even after 1 year of incubation. Through the ammonification process, dissolved organic matter (DOM) from cyanobacterial lysate was converted to ammonium which was used as an energy source for Thaumarchaeota to fix inorganic carbon into biomass. Our study further advocates the important roles of Thaumarchaeota in the ocean’s biogeochemical cycle. 

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5. A Conserved Structural Role for the Walker-A Lysine in P-Loop Containing Kinases

   https://doi.org/10.3389/fmolb.2021.747206  

   Hajredini, Fatlum; Ghose, Ranajeet (October 2021, Frontiers in Molecular Biosciences)

   Bacterial tyrosine kinases (BY-kinases) and shikimate kinases (SKs) comprise two structurally divergent P-loop containing enzyme families that share similar catalytic site geometries, most notably with respect to their Walker-A, Walker-B, and DxD motifs. We had previously demonstrated that in BY-kinases, a specific interaction between the Walker-A and Walker-B motifs, driven by the conserved “catalytic” lysine housed on the former, leads to a conformation that is unable to efficiently coordinate Mg 2+ •ATP and is therefore incapable of chemistry. Here, using enhanced sampling molecular dynamics simulations, we demonstrate that structurally similar interactions between the Walker-A and Walker-B motifs, also mediated by the catalytic lysine, stabilize a state in SKs that deviates significantly from one that is necessary for the optimal coordination of Mg 2+ •ATP. This structural role of the Walker-A lysine is a general feature in SKs and is found to be present in members that encode a Walker-B sequence characteristic of the family ( Coxiella burnetii SK), and in those that do not ( Mycobacterium tuberculosis SK). Thus, the structural role of the Walker-A lysine in stabilizing an inactive state, distinct from its catalytic function, is conserved between two distantly related P-loop containing kinase families, the SKs and the BY-kinases. The universal conservation of this element, and of the key characteristics of its associated interaction partners within the Walker motifs of P-loop containing enzymes, suggests that this structural role of the Walker-A lysine is perhaps a widely deployed regulatory mechanism within this ancient family. 

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