Structure and electron transfer pathways of an electron-bifurcating NiFe-hydrogenase

Feng, Xinwei; Schut, Gerrit J.; Haja, Dominik K.; Adams, Michael W. W.; H, Li

doi:10.1126/sciadv.abm7546

Cited by 24 publications

(41 citation statements)

References 60 publications

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“…Bifurcating FeFe-hydrogenases contain three subunits designated HydABC, where HydA contains the catalytic H cluster, the site of reversible H 2 activation. Bifurcating NiFe-hydrogenases also contain homologs of HydABC, where the catalytic H cluster of the FeFe-enzyme is replaced by a [4Fe-4S] cluster, and one of the two additional subunits (HydSL) contain the catalytic NiFe-site (Feng et al, 2022). As shown in Figure 1, in the structurally characterized NiFe-enzyme, HydA and HydB each contain five iron-sulfur clusters, designated A1-A5 and B1-B5, respectively, while HydC contains a single cluster (C1).…”

Section: Phylogeny Of the Hydabc Familymentioning

confidence: 99%

“…As shown in Figure 1, in the structurally characterized NiFe-enzyme, HydA and HydB each contain five iron-sulfur clusters, designated A1-A5 and B1-B5, respectively, while HydC contains a single cluster (C1). HydB also contains the flavin (FMN) that binds NAD(H) and this subunit also binds Fd (Feng et al, 2022). Herein we have carried out a detailed comparative genome analysis and found that the two HydABC subunits of these two hydrogenases are highly conserved in anaerobic microorganisms.…”

Section: Phylogeny Of the Hydabc Familymentioning

confidence: 99%

“…Hence FMN plays a very complex role in FeFe-hydrogenases and this must be very different from the straightforward role of the BF-FADs in other three types of electron bifurcating enzyme. Insights into the electron bifurcation mechanism of the FeFe-hydrogenases were recently provided by the cryo-EM structure of a related electron bifurcating NiFe-hydrogenase termed NiFe-HydABCSL (Feng et al, 2022). This enzyme was purified in its active electron bifurcating form from native biomass of the moderately thermophilic bacterium (T max 60 • C) Acetomicrobium mobile.…”

Section: Introductionmentioning

confidence: 99%

“…1) was proposed to be achieved by the combination of the single FMN in a unique arrangement of nearby iron sulfur clusters. Although the exact mechanism was not known, it was clear that significant conformational changes were involved and bifurcation ready and post bifurcation conformational states were identified (Feng et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, some of these Bfu enzymes are predicted to be integral membrane complexes capable of proton-pumping. Based on the structure of the bifurcating HydABCSL NiFe-hydrogenase (Feng et al, 2022), we have categorized the Bfu family members into four structural types based on their pathways of electron transfer to the bifurcating BfuBC core. Moreover, we hypothesize that they all use a new type of mechanism for electron bifurcation involving a single flavin in combination with three iron-sulfur clusters that is independent of the third substrate that they utilize.…”

Section: Introductionmentioning

confidence: 99%

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An Abundant and Diverse New Family of Electron Bifurcating Enzymes With a Non-canonical Catalytic Mechanism

et al. 2022

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Microorganisms utilize electron bifurcating enzymes in metabolic pathways to carry out thermodynamically unfavorable reactions. Bifurcating FeFe-hydrogenases (HydABC) reversibly oxidize NADH (E′∼−280 mV, under physiological conditions) and reduce protons to H2 gas (E°′−414 mV) by coupling this endergonic reaction to the exergonic reduction of protons by reduced ferredoxin (Fd) (E′∼−500 mV). We show here that HydABC homologs are surprisingly ubiquitous in the microbial world and are represented by 57 phylogenetically distinct clades but only about half are FeFe-hydrogenases. The others have replaced the hydrogenase domain with another oxidoreductase domain or they contain additional subunits, both of which enable various third reactions to be reversibly coupled to NAD+ and Fd reduction. We hypothesize that all of these enzymes carry out electron bifurcation and that their third substrates can include hydrogen peroxide, pyruvate, carbon monoxide, aldehydes, aryl-CoA thioesters, NADP+, cofactor F420, formate, and quinones, as well as many yet to be discovered. Some of the enzymes are proposed to be integral membrane-bound proton-translocating complexes. These different functionalities are associated with phylogenetically distinct clades and in many cases with specific microbial phyla. We propose that this new and abundant class of electron bifurcating enzyme be referred to as the Bfu family whose defining feature is a conserved bifurcating BfuBC core. This core contains FMN and six iron sulfur clusters and it interacts directly with ferredoxin (Fd) and NAD(H). Electrons to or from the third substrate are fed into the BfuBC core via BfuA. The other three known families of electron bifurcating enzyme (abbreviated as Nfn, EtfAB, and HdrA) contain a special FAD that bifurcates electrons to high and low potential pathways. The Bfu family are proposed to use a different electron bifurcation mechanism that involves a combination of FMN and three adjacent iron sulfur clusters, including a novel [2Fe-2S] cluster with pentacoordinate and partial non-Cys coordination. The absolute conservation of the redox cofactors of BfuBC in all members of the Bfu enzyme family indicate they have the same non-canonical mechanism to bifurcate electrons. A hypothetical catalytic mechanism is proposed as a basis for future spectroscopic analyses of Bfu family members.

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Section: Phylogeny Of the Hydabc Familymentioning

confidence: 99%

Section: Phylogeny Of the Hydabc Familymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An Abundant and Diverse New Family of Electron Bifurcating Enzymes With a Non-canonical Catalytic Mechanism

et al. 2022

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Structures and Electron Transport Paths in the Four Families of Flavin-Based Electron Bifurcation Enzymes

Feng,

Schut,

Adams

et al. 2024

Subcellular Biochemistry

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Metatranscriptomic insights into the microbial electrosynthesis of acetate by Fe2+/Ni2+ addition

Zhang

et al. 2023

World J Microbiol Biotechnol

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As important components of enzymes and coenzymes involved in energy transfer and Wood-Ljungdahl (WL) pathways, Fe 2+ and Ni 2+ supplementation may promote the acetate synthesis through CO 2 reduction by the microbial electrosynthesis (MES). However, the effect of Fe 2+ and Ni 2+ addition on acetate production in MES and corresponding microbial mechanisms have not been fully studied.Therefore, this study investigated the effect of Fe 2+ and Ni 2+ addition on acetate production in MES, and explored the underlying microbial mechanism from the metatranscriptomic perspective. Both Fe 2+ and Ni 2+ addition enhanced acetate production of the MES, which was 76.9% and 110.9% higher than that of control, respectively. Little effect on phylum level and small changes in genus-level microbial composition was caused by Fe 2+ and Ni 2+ addition. Gene expression of 'Energy metabolism', especially in 'Carbon xation pathways in prokaryotes' was up-regulated by Fe 2+ and Ni 2+ addition. Hydrogenase was found as an important energy transfer mediator for CO 2 reduction and acetate synthesis. Fe 2+ addition and Ni 2+ addition respectively enhanced the expression of methyl branch and carboxyl branch of the WL pathway, and thus promoted acetate production. The study provided a metatranscriptomic insight into the effect of Fe 2+ and Ni 2+ on acetate production by CO 2 reduction in MES. HighlightsAcetate microbial electrosynthesis was enhanced by Fe 2+ and Ni 2+ addition.Fe 2+ and Ni 2+ addition caused small changes in genus-level microbial composition.Genes expression of hydrogenase was increased with Fe 2+ and Ni 2+ addition.Fe 2+ improved methyl and Ni 2+ improved carboxyl branch expression of WL pathway.

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Structure and electron transfer pathways of an electron-bifurcating NiFe-hydrogenase

Cited by 24 publications

References 60 publications

An Abundant and Diverse New Family of Electron Bifurcating Enzymes With a Non-canonical Catalytic Mechanism

An Abundant and Diverse New Family of Electron Bifurcating Enzymes With a Non-canonical Catalytic Mechanism

Structures and Electron Transport Paths in the Four Families of Flavin-Based Electron Bifurcation Enzymes

Metatranscriptomic insights into the microbial electrosynthesis of acetate by Fe2+/Ni2+ addition

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