Direct coupling of lactate oxidation with butyryl-CoA formation via a canonical electron transfer flavoprotein in Fusobacterium nucleatum
Bibliographic record
Abstract
The gram-negative opportunistic pathogen Fusobacterium nucleatum encodes an electron transfer flavoprotein (ETF) within a 6-gene cluster that also includes genes for a D-lactate dehydrogenase (Ldh), butyryl-CoA dehydrogenase (Bcd), and LrgAB. Herein, we demonstrate that ETF functions as a canonical ETF, transferring two electrons from Ldh following oxidation of D-lactate to Bcd for the reduction of crotonyl-CoA to butyryl-CoA. Steady-state kinetic analysis of the Ldh FN /ETF FN /Bcd FN reaction (lactate + crotonyl-CoA → pyruvate + butyryl-CoA) yielded a k cat of 2.5 ± 0.1 s -1 and a K M of 0.65 ± 0.04 μM and 5.2 ± 0.5 μM for D-lactate and butyryl-CoA, respectively. As observed in homologous ETFs, the FAD cofactor of ETF forms the red anionic semiquinone (FAD •- ) but the E o ′ values (versus the normal hydrogen electrode) of -70 mV (FAD/FAD •- ) and=-122 mV (FAD •- /FADH - ) are more compressed and negative compared to other ETFs, indicating the flavoprotein is physiologically primed to accept two electrons from Ldh. Similarly, reductive titration of Ldh shows that its FAD cofactor also forms the red anionic semiquinone, but the E o ′ values for FAD/FAD •- (-109 mV) and FAD •- /FADH - (-115 mV) are even more closely spaced. We discuss how F. nucleatum potentially uses this lactate utilization gene cluster to maintain redox homeostasis during oxidative stress and how beneficial gut anaerobes of the Lachnospiraceae family with similar gene clusters employ either a canonical or bifurcating ETF for the conversion of lactate (and acetate) to butyrate.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".