Mechanistic insights into energy conservation by flavin-based electron bifurcation

Abstract

The recently realized biochemical phenomenon of energy conservation through electron bifurcation provides biology with an elegant means to maximize utilization of metabolic energy. The mechanism of coordinated coupling of exergonic and endergonic oxidation-reduction reactions by a single enzyme complex has been elucidated through optical and paramagnetic spectroscopic studies revealing unprecedented features. Pairs of electrons are bifurcated over more than 1 volt of electrochemical potential by generating a low-potential, highly energetic, unstable flavin semiquinone and directing electron flow to an iron-sulfur cluster with a highly negative potential to overcome the barrier of the endergonic half reaction. The unprecedented range of thermodynamic driving force that is generated by flavin-based electron bifurcation accounts for unique chemical reactions that are catalyzed by these enzymes.

Hydrogen Deuterium Exchange Mass Spectrometry of Oxygen Sensitive Proteins

“…Some of these proteins provide an alternative supply of energy to anaerobic microbes through a process known as Flavin-based electron bifurcation (FBEB) (Lubner et al ., 2017). FBEB generates reduced ferredoxin, which can be oxidized to produce energy.…”

“…FBEB generates reduced ferredoxin, which can be oxidized to produce energy. Proteins that are capable of reducing ferredoxin are of great interest and have been the focus of recent studies using HDX-MS (Demmer et al ., 2016; Lubner et al ., 2017; Berry et al ., 2018). HDX-MS is a powerful technique for investigating protein stability, dynamics, and ligand binding providing information about the relationship between structure and function.…”

“…The Mass Spectrometry Facility at MSU was supported in part by the Murdock Charitable Trust and an NIH IDEA program grant P20GM103474. The work detailed in this protocol was adapted from work described in recent publications (Lubner et al ., 2017; Berry et al ., 2018). The authors declare that they do not have any conflicts of interest.…”

Electron Bifurcation Makes the Puzzle Pieces Fall Energetically into Place in Methanogenic Energy Conservation

“…Cattle basically consumef ood that their bodies cannotd igest without the activity of microbes. [5,6] Flavin-based electron bifurcationa ppears to be establishing exciting new paradigms in biological electron transfer.Heterodisulfide reductase (Hdr) is the valve that closes the cycle of methanogenesis (Figure 1), allowing energy to be conserveda nd providing an energetic advantage to the cell. Methanogens use electrons from the oxidation of hydrogen to sequentially ratchet carbon througha ll eight of its oxidation states throught he initial activation of carbon dioxide to af ormylc onjugate of an organic cofactor called methanofuran.…”

“…Further C1 reduced states are generated enzymatically in conjugates of another organic cofactor called tetrahydromethanopterin, where finally am ethyl group is transferredt othe smallest known organic cofactor termedm ercaptoethane sulfonate (coenzyme M, CoM). [5,13] In fact, prior to as tructure, it was once thought that what we now know as the bifurcating flavin was not the site of bifurcation. This is the penultimatec onserved step in all pathways of methanogenesis leaving only the reduction of CoM-S-S-CoB and recycling of the key methanogen cofactors CoM and CoB.…”