Characterization of Methyl- and Acetyl-Ni Intermediates in Acetyl CoA Synthase Formed during Anaerobic CO2 and CO Fixation

The Wood–Ljungdahl Pathway is a unique biological mechanism of carbon dioxide and carbon monoxide fixation proposed to operate through nickel-based organometallic intermediates. The most unusual steps in this metabolic cycle involve a complex of two distinct nickel–iron–sulfur proteins: CO dehydrogenase and acetyl-CoA synthase (CODH/ACS). Here, we describe the nickel-methyl and nickel-acetyl intermediates in ACS completing the characterization of all its proposed organometallic intermediates. A single nickel site (Nip) within the A cluster of ACS undergoes major geometric and redox changes as it transits the planar Nip, tetrahedral Nip–CO and planar Nip–Me and Nip–Ac intermediates. We propose that the Nip intermediates equilibrate among different redox states, driven by an electrochemical–chemical (EC) coupling process, and that geometric changes in the A-cluster linked to large protein conformational changes control entry of CO and the methyl group.

• Publication year

  2023

• Venue

  Journal of the American Chemical Society

• Publication date

  2023-06-12

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1021/jacs.3c01772PMID 37306669PMCID 10311460
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Thioester synthesis by a designed nickel enzyme models prebiotic energy conversion

  2022cited by this paper
• Theoretical Study on Redox Potential Control of Iron-Sulfur Cluster by Hydrogen Bonds: A Possibility of Redox Potential Programming

  2021cited by this paper
• Ligand Field Inversion as a Mechanism to Gate Bioorganometallic Reactivity: Investigating a Biochemical Model of Acetyl CoA Synthase Using Spectroscopy and Computation.

  2021cited by this paper
• Stepwise Iodide-Free Methanol Carbonylation via Methyl Acetate Activation by Pincer Iridium Complexes.

  2021cited by this paper
• 13C Electron Nuclear Double Resonance Spectroscopy Shows Acetyl-CoA Synthase Binds Two Substrate CO in Multiple Binding Modes and Reveals the Importance of a CO-Binding ‘Alcove’

  2020cited by this paper
• The ORCA quantum chemistry program package.

  2020cited by this paper
• Crystallographic Characterization of the Carbonylated A-Cluster in Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase

  2020cited by this paper
• Negative-Stain Electron Microscopy Reveals Dramatic Structural Rearrangements in Ni-Fe-S-Dependent Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase.

  2020cited by this paper
• A Biochemical Nickel(I) State Supports Nucleophilic Alkyl Addition: A Roadmap for Methyl Reactivity in Acetyl Coenzyme A Synthase

  2019cited by this paper
• Comparative electronic structures of nitrogenase FeMoco and FeVco

  2017cited by this paper
• Multielectron Chemistry within a Model Nickel Metalloprotein: Mechanistic Implications for Acetyl-CoA Synthase.

  2017cited by this paper
• X-ray Absorption Spectroscopy Reveals an Organometallic Ni-C Bond in the CO-Treated Form of Acetyl-CoA Synthase.

  2017influential reference
• Ligand binding at the A-cluster in full-length or truncated acetyl-CoA synthase studied by X-ray absorption spectroscopy

  2017cited by this paper
• The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase

  2016cited by this paper
• The physiology and habitat of the last universal common ancestor

  2016cited by this paper
• Extended X-ray absorption fine structure and multiple-scattering simulation of nickel dithiolene complexes Ni[S2C2(CF3)2]2(n) (n = -2, -1, 0) and an olefin adduct Ni[S2C2(CF3)2]2(1-hexene).

  2015cited by this paper
• Structure, Function, and Mechanism of the Nickel Metalloenzymes, CO Dehydrogenase, and Acetyl-CoA Synthase

  2014cited by this paper
• Iron–sulfur bond covalency from electronic structure calculations for classical iron–sulfur clusters

  2014cited by this paper
• Light-atom influences on the electronic structures of iron-sulfur clusters.

  2014cited by this paper
• Low-energy spectrum of iron-sulfur clusters directly from many-particle quantum mechanics.

  2014cited by this paper
• X-ray absorption near-edge spectroscopy in bioinorganic chemistry: Application to M-O2 systems.

  2013cited by this paper
• X-ray absorption spectroscopic investigation of the electronic structure differences in solution and crystalline oxyhemoglobin

  2013cited by this paper
• Different modes of carbon monoxide binding to acetyl-CoA synthase and the role of a conserved phenylalanine in the coordination environment of nickel.

  2013cited by this paper
• Redox potentials and protonation of the A-cluster from acetyl-CoA synthase. A density functional theory study.

  2013cited by this paper
• Evidence that ferredoxin interfaces with an internal redox shuttle in Acetyl-CoA synthase during reductive activation and catalysis.

  2011cited by this paper
• S K-edge XAS and DFT calculations on SAM dependent pyruvate formate-lyase activating enzyme: nature of interaction between the Fe4S4 cluster and SAM and its role in reactivity.

  2011cited by this paper
• Infrared and EPR spectroscopic characterization of a Ni(I) species formed by photolysis of a catalytically competent Ni(I)-CO intermediate in the acetyl-CoA synthase reaction.

  2010cited by this paper
• Geometric and electronic structure and reactivity of a mononuclear "side-on" nickel(III)-peroxo complex.

  2009cited by this paper
• Dinuclear nickel complexes modeling the structure and function of the acetyl CoA synthase active site

  2009cited by this paper
• Two separate one-electron steps in the reductive activation of the A cluster in subunit beta of the ACDS complex in Methanosarcina thermophila.

  2008cited by this paper
• Mossbauer evidence for an exchange-coupled {[Fe4S4]1+ Nip1+} A-cluster in isolated alpha subunits of acetyl-coenzyme A synthase/carbon monoxide dehydrogenase.

  2008cited by this paper
• Xenon in and at the end of the tunnel of bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase.

  2008cited by this paper
• Delving into the complex picture of Ti(IV)–citrate speciation in aqueous media: Synthetic, structural, and electrochemical considerations in mononuclear Ti(IV) complexes containing variably deprotonated citrate ligands

  2008cited by this paper
• Pulse-Chase Studies of the Synthesis of Acetyl-CoA by Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase

  2008cited by this paper
• Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation.

  2008cited by this paper
• Description of the ground-state covalencies of the bis(dithiolato) transition-metal complexes from X-ray absorption spectroscopy and time-dependent density-functional calculations.

  2007cited by this paper
• PySpline: A Modern, Cross‐Platform Program for the Processing of Raw Averaged XAS Edge and EXAFS Data

  2007cited by this paper
• Ni K-edge XAS suggests that coordination of Ni(II) to the unstructured amyloidogenic region of the human prion protein produces a Ni(2) bis-mu-hydroxo dimer.

  2007cited by this paper
• Formation of a nickel-methyl species in methyl-coenzyme m reductase, an enzyme catalyzing methane formation.

  2007cited by this paper
• Sulfur K-edge X-ray absorption spectroscopy as a probe of ligand-metal bond covalency: metal vs ligand oxidation in copper and nickel dithiolene complexes.

  2007cited by this paper
• On the accuracy of density functional theory for iron—sulfur clusters

  2006cited by this paper
• Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella thermoacetica.

  2006cited by this paper
• Picosecond X-ray absorption spectroscopy of a photoinduced iron(II) spin crossover reaction in solution.

  2006cited by this paper
• Kinetics of CO insertion and acetyl group transfer steps, and a model of the acetyl-CoA synthase catalytic mechanism.

  2006cited by this paper
• Mössbauer and EPR study of recombinant acetyl-CoA synthase from Moorella thermoacetica.

  2006cited by this paper
• ATHENA, ARTEMIS, HEPHAESTUS: data analysis for X-ray absorption spectroscopy using IFEFFIT.

  2005cited by this paper
• Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy.

  2005cited by this paper
• Sulfur K-edge XAS and DFT calculations on [Fe4S4]2+ clusters: effects of H-bonding and structural distortion on covalency and spin topology.

  2005cited by this paper
• The A-Cluster in Subunit β of the Acetyl-CoA Decarbonylase/Synthase Complex from Methanosarcina thermophila: Ni and Fe K-Edge XANES and EXAFS Analyses [J. Am. Chem. Soc. 2003, 125, 15343−15351].

  2004cited by this paper
• A functional Ni-Ni-[4Fe-4S] cluster in the monomeric acetyl-CoA synthase from Carboxydothermus hydrogenoformans.

  2004cited by this paper
• Acetyl-coenzyme A synthase: the case for a Nip0-based mechanism of catalysis

  2004cited by this paper
• Evidence that NiNi acetyl-CoA synthase is active and that the CuNi enzyme is not.

  2004cited by this paper
• Description of the ground state wave functions of Ni dithiolenes using sulfur K-edge X-ray absorption spectroscopy.

  2003cited by this paper
• Ni-Zn-[Fe4-S4] and Ni-Ni-[Fe4-S4] clusters in closed and open α subunits of acetyl-CoA synthase/carbon monoxide dehydrogenase

  2003cited by this paper
• A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/ Acetyl-CoA Synthase

  2002cited by this paper
• Rapid kinetic studies of acetyl-CoA synthesis: evidence supporting the catalytic intermediacy of a paramagnetic NiFeC species in the autotrophic Wood-Ljungdahl pathway.

  2002cited by this paper
• Acetyl coenzyme A synthesis from unnatural methylated corrinoids: requirement for "base-off" coordination at cobalt.

  2001cited by this paper
• A Systematic K-edge X-ray Absorption Spectroscopic Study of Cu(III) Sites

  2000cited by this paper
• Redox-dependent acetyl transfer partial reaction of the acetyl-CoA decarbonylase/synthase complex: kinetics and mechanism.

  1998cited by this paper
• METHYLATION OF CARBON MONOXIDE DEHYDROGENASE FROM CLOSTRIDIUM THERMOACETICUM AND MECHANISM OF ACETYL COENZYME A SYNTHESIS

  1997cited by this paper
• Multiple-scattering calculations of x-ray-absorption spectra.

  1995cited by this paper
• Transition-metal complexes with sulfur ligands. Part LXXXIV. CH3 complexes with [NiS] fragments as models for CO dehydrogenase. Synthesis and properties of [Ni(‘MeS2’)2] and (NMe4)[Ni(CH3)(‘MeS2’)2] (‘MeS2’−=o-(methylthio)thiophenolate(1−))

  1992influential reference
• Characterization of the NiFeCO complex of carbon monoxide dehydrogenase as a catalytically competent intermediate in the pathway of acetyl-coenzyme A synthesis.

  1991cited by this paper
• Reductive activation of the coenzyme A/acetyl-CoA isotopic exchange reaction catalyzed by carbon monoxide dehydrogenase from Clostridium thermoaceticum and its inhibition by nitrous oxide and carbon monoxide.

  1991cited by this paper
• Ligand spin densities in blue copper proteins by q-band proton and nitrogen-14 ENDOR spectroscopy

  1991cited by this paper
• X-ray spectroscopic studies of nickel complexes, with application to the structure of nickel sites in hydrogenases

  1991cited by this paper
• Theoretical X-ray Absorption Fine Structure Standards

  1991cited by this paper
• Controlled potential enzymology of methyl transfer reactions involved in acetyl-CoA synthesis by CO dehydrogenase and the corrinoid/iron-sulfur protein from Clostridium thermoaceticum.

  1990cited by this paper
• CO dehydrogenase from Clostridium thermoaceticum. EPR and electrochemical studies in CO2 and argon atmospheres.

  1990cited by this paper
• Acetyl-CoA pathway of autotrophic growth. Identification of the methyl-binding site of the CO dehydrogenase.

  1988cited by this paper
• Mössbauer, EPR, and optical studies of the corrinoid/iron-sulfur protein involved in the synthesis of acetyl coenzyme A by Clostridium thermoaceticum.

  1987cited by this paper
• ENDOR of the Resting State of Nitrogenase Molybdenum

  1986cited by this paper
• Convenient synthesis and properties of (R4N)2[Ni(SAr)4] (Ar = C6H5, p-C6H4Cl, p-C6H4CH3, and m-C6H4Cl) and the structure of tetraethylammonium tetrakis(p-chlorobenzenethiolato)nickelate(II)

  1986cited by this paper
• Acetate biosynthesis by acetogenic bacteria. Evidence that carbon monoxide dehydrogenase is the condensing enzyme that catalyzes the final steps of the synthesis.

  1985cited by this paper
• EXAFS and Near Edge Structure III

  1984cited by this paper
• The inactivation of yeast enolase by 2,3-butanedione.

  1978cited by this paper
• Significance tests on the crystallographic R factor

  1965cited by this paper
• Digital Commons @ Trinity Digital Commons @ Trinity

  year unknowncited by this paper

• Bidirectional extracellular electron transfer and electroautotrophic metabolism in Fundidesulfovibrio terrae

  2026cites this paper
• Mechanistic Aspects of Thioester Formation by Binuclear Nickel(II)-thiolate as a Functional Model of the Nip Site of Acetyl-CoA Synthase.

  2026cites this paper
• Catching carbon fixation without fixing.

  2025cites this paper
• Conformational dynamics of a multienzyme complex in anaerobic carbon fixation.

  2025cites this paper
• The mechanism of acetyl-CoA synthase through the lens of a nickel model system

  2025influential citation
• Ligand binding to a Ni–Fe cluster orchestrates conformational changes of the CO-dehydrogenase–acetyl-CoA synthase complex

  2025influential citation
• Mixed-valency in multinuclear nickel complexes: From fundamentals to nickel enzymes.

  2025cites this paper
• Recent Progress in CO2 Conversion: An Overview of Catalytic Strategies for Sustainable Fuel and Chemical Synthesis

  2025cites this paper
• Evidence for corrin biosynthesis in the last universal common ancestor

  2024cites this paper
• Conversion of pyridoxal to pyridoxamine with NH 3 and H 2 on nickel generates a protometabolic nitrogen shuttle under serpentinizing conditions

  2024cites this paper
• Site specific redox properties in ligand differentiated di-nickel complexes inspired by the acetyl CoA synthase active site.

  2024cites this paper
• Coupling CO2 Reduction and Acetyl-CoA Formation: The Role of a CO Capturing Tunnel in Enzymatic Catalysis.

  2024cites this paper
• An alcove at the acetyl-CoA synthase nickel active site is required for productive substrate CO binding and anaerobic carbon fixation

  2024cites this paper
• Mixed Valence {Ni2+Ni1+} Clusters as Models of Acetyl Coenzyme A Synthase Intermediates

  2024cites this paper
• Chemical Antiquity in Metabolism

  2024cites this paper
• Snapshots of acetyl-CoA synthesis, the final step of CO2 fixation in the Wood-Ljungdahl pathway

  2024cites this paper
• Capturing a methanogenic carbon monoxide dehydrogenase/acetyl-CoA synthase complex via cryogenic electron microscopy

  2024cites this paper
• Visualizing the Mechanism of an Ancient Pathway in the Carbon Cycle

  2023cites this paper
• Gravitational Induced Chirality of Biology by Nuclear Magnetic Moments of 13 C and 17 O with 1 H, 14 N, and 25 Mg

  2023cites this paper