Nitratidesulfovibrio vulgaris Pathways Project

Bottom line: Nitratidesulfovibrio (formerly Desulfovibrio) vulgaris
Hildenborough is the model sulfate-reducing bacterium, and its genes are
annotated almost entirely by electronic pipelines. We reviewed genes in four
pathways: sulfate reduction (6), potassium transport (7), sigma factors (5)
and hydrogen metabolism (5 representative hydrogenase subunits). Twenty of
the 23 reviews are done, covering 180 annotation rows: 80 accepted, 32
modified, 15 removed, 11 marked over-annotated, 5 kept as non-core and 37
proposed as NEW. The hysA, echA and cooH reviews are stubs with all rows
still PENDING; hydA and hynA1 are reviewed, although the status checklist
below leaves all five hydrogenases unticked. The main corrections split
catalytic from accessory subunits: AprB and KdpC lose catalytic terms in
favour of electron transfer and ATPase activator activity, the TrkA-type RCK
proteins become potassium channel regulators rather than transporters, sigma
factors get sigma factor activity instead of DNA-binding transcription
factor activity, and DVU3336 turns out to carry only the KdpD sensor domain,
with the histidine kinase on the neighbouring DVU3335. The input list also
put rpoC, an RNA polymerase core subunit, among the sigma factors. An earlier
reassignment of DVU0848 and DVU0849 from QmoA/QmoB to the Flx–Hdr bifurcating
complex was wrong and is reverted in
PR #3226: the genes
sit in the aprBA–qmoABC cluster (DVU0846–0850), while Flx–Hdr is encoded at
DVU2399–2405. Once #3226 merges, QmoB loses two unsupported NEW rows
(178 rows, 35 NEW).

Overview

This project focuses on reviewing gene annotations for key pathways in Nitratidesulfovibrio vulgaris (formerly Desulfovibrio vulgaris, strain Hildenborough). This sulfate-reducing bacterium is a model organism for studying anaerobic respiration using sulfate as the terminal electron acceptor.

Model Organism

Species: Nitratidesulfovibrio vulgaris (strain Hildenborough)

• UniProt species code: DESVH (note: still uses old Desulfovibrio vulgaris code)
• NCBI Taxonomy ID: 882
• Genome: NC_002937.3
• Key metabolism: Dissimilatory sulfate reduction, hydrogen cycling

Pathway 1: Sulfate Reduction

The dissimilatory sulfate reduction pathway is the core energy metabolism of this organism. Sulfate is reduced to sulfide in a multi-step process:

1. Sulfate uptake - via sulfate permeases
2. Sulfate activation - ATP sulfurylase generates adenylyl-sulfate (APS)
3. APS reduction - APS reductase (AprAB) reduces APS to sulfite
4. Electron transfer - QmoABC complex links APS reduction to quinone pool

Genes for Review

Pathway 2: Potassium Transport

Potassium homeostasis is critical for maintaining membrane potential and osmotic balance.

Genes for Review

Pathway 3: Sigma Factors

Sigma factors regulate gene expression by directing RNA polymerase to specific promoters.

Genes for Review

Pathway 4: Hydrogen Metabolism

D. vulgaris Hildenborough possesses multiple hydrogenases for hydrogen cycling, which is central to its energy metabolism. The organism has four periplasmic hydrogenases for H2 uptake and two membrane-bound cytoplasmic hydrogenases for H2 production.

Periplasmic Hydrogenases (H2 Uptake)

Membrane-Bound Cytoplasmic Hydrogenases (H2 Production)

Genes for Initial Review (Representative Subunits)

Key References

• Genome of D. vulgaris Hildenborough (PMID:15077118)
• Sulfate reduction pathway review (PMID:24106043)
• QmoABC complex characterization (PMID:15304518)
• Function of Periplasmic Hydrogenases (PMID:17586632)
• NiFeSe hydrogenase characterization (PMID:16187073)
• Fe-only hydrogenase deletion effects (PMID:11790737)

STATUS

Sulfate Reduction Pathway (Priority 1) - COMPLETED

• [x] aprB (Q72DT3) - APS reductase beta subunit (electron transfer)
• [x] aprA (Q72DT2) - APS reductase alpha subunit (catalytic FAD-containing)
• [x] qmoA (Q72DT1) - QmoA, soluble HdrA-like FAD subunit of QmoABC (identity restored in PR #3226)
• [x] qmoB (Q72DT0) - QmoB, HdrA-like iron-sulfur flavoprotein with an MvhD-like domain (identity restored in PR #3226)
• [x] qmoC (Q72DS9) - Membrane subunit of QmoABC complex
• [x] DVU0279 (Q72FD5) - SulP/SLC26 family transporter (likely dicarboxylate, not sulfate)

Sigma Factors (Priority 3) - COMPLETED

• [x] rpoH (Q72BQ0) - Sigma-32 heat shock factor (RpoH)
• [x] rpoN (Q72BK7) - Sigma-54 factor (RpoN)
• [x] rpoD (Q72B50) - Sigma-70 housekeeping factor (RpoD)
• [x] rpoC (Q727C6) - RNA polymerase beta' subunit (NOT a sigma factor!)
• [x] fliA (Q726C4) - Sigma-28 flagellar factor (FliA)

Potassium Transport (Priority 2) - COMPLETED

• [x] DVU1606 (Q72BM9) - TrkA family RCK regulatory subunit
• [x] DVU3335 (Q725U0) - KdpD-associated histidine kinase sensor
• [x] kdpD (Q725T9) - KdpD tandem kinase (His + Ser kinase)
• [x] kdpC (Q725T8) - KdpC catalytic chaperone subunit
• [x] kdpB (Q725T7) - KdpB P-type ATPase catalytic subunit
• [x] DVU0412 (Q72F06) - TrkA-type RCK regulatory subunit
• [x] trkH (Q72F05) - TrkH membrane channel pore

Hydrogen Metabolism (Priority 4) - IN PROGRESS

• [ ] hydA (P07598) - [Fe] hydrogenase large subunit (periplasmic)
• [ ] hysA (Q72AS3) - [NiFeSe] hydrogenase large subunit (periplasmic)
• [ ] hynA1 (Q72AS0) - [NiFe] hydrogenase 1 large subunit (periplasmic)
• [ ] echA (Q72EY4) - Ech hydrogenase subunit A (cytoplasmic membrane-bound)
• [ ] cooH (Q729Q8) - Coo hydrogenase CooH subunit (cytoplasmic membrane-bound)

NOTES

2026-01-15

Project created. Compiled gene list for three pathways in Nitratidesulfovibrio vulgaris (Hildenborough):

1. Sulfate reduction pathway (6 genes) - Core energy metabolism
2. APS reductase complex (AprAB): DVU0846-0847
3. QmoABC complex: DVU0848-0850

4. Sulfate permease: DVU0279

5. Potassium transport (7 genes) - Ion homeostasis

6. TrkA/TrkH systems: DVU0412-0413, DVU1606
7. Kdp system (ATP-driven): DVU3336-3338

8. Regulatory kinase: DVU3335

9. Sigma factors (5 genes) - Transcriptional regulation

10. Housekeeping (RpoD), heat shock (RpoH), nitrogen (RpoN), flagellar (FliA)
11. Note: RpoC is RNA polymerase subunit, not a sigma factor

Priority: Start with sulfate reduction pathway as this is the defining metabolic feature of this organism.

All UniProt IDs retrieved from UniProt REST API using DVU locus tags. Note that the organism name has been updated from Desulfovibrio vulgaris to Nitratidesulfovibrio vulgaris but UniProt IDs remain valid.

Sulfate Reduction Pathway Reviews Completed:

Key findings from annotation reviews:

1. AprAB (APS Reductase):
2. aprB (Q72DT3): Beta subunit with two [4Fe-4S] clusters. Core function is electron transfer (GO:0009055), not catalytic activity. Modified GO:0009973 (adenylyl-sulfate reductase activity) to electron transfer activity since AprB is the electron relay, not the catalytic subunit.

3. aprA (Q72DT2): Alpha subunit containing FAD. This is the catalytic subunit. Accepted GO:0009973 (adenylyl-sulfate reductase activity). Added GO:0019420 (dissimilatory sulfate reduction).

4. DVU0848-0850 (QmoABC):

5. Correction (2026-09, PR #3226): the first reviews reassigned DVU0848 and DVU0849 to the FlxABCD-HdrABC bifurcating complex. That was wrong: DVU0846-0850 is the aprBA-qmoABC cluster, and Flx-Hdr is encoded at DVU2399-2405. The Flx-Hdr claims came from deep-research files and a thesis about the Flx-Hdr complex; #3226 restores QmoA/QmoB and re-grounds the rows in the Qmo literature.
6. DVU0848 (Q72DT1): QmoA, a soluble HdrA-like FAD protein; the subunit reported to contact AprAB.
7. DVU0849 (Q72DT0): QmoB, a soluble HdrA-like iron-sulfur flavoprotein with a C-terminal MvhD/FlpD-like domain. Its AP-MS partner Q72DS8 (DVU0851) is QmoD, not HdrC.

8. DVU0850 (Q72DS9): QmoC, the membrane-integral subunit with heme b groups that exchanges electrons with the menaquinone pool.

9. DVU0279 (Q72FD5) - Sulfate Permease?:

10. ANNOTATION CONCERN: Despite being annotated as "sulfate permease family protein", the SulP/SLC26 family is functionally diverse. Many members transport dicarboxylates, bicarbonate, or other anions rather than sulfate. The annotation GO:0055085 (transmembrane transport) was accepted but sulfate-specific transport needs experimental verification.

Sigma Factor Pathway Reviews Completed:

Key findings from annotation reviews:

1. rpoC (Q727C6) is NOT a sigma factor:

2. CRITICAL CORRECTION: rpoC encodes the RNA polymerase beta' (β') subunit, which is the DNA-binding core subunit of RNAP - NOT a sigma factor. This was incorrectly listed in the original gene set. RpoC provides DNA template binding and forms part of the catalytic core enzyme.

3. Sigma factor family classification:

4. rpoH (Q72BQ0): Sigma-32 family (σ32), heat shock response
5. rpoN (Q72BK7): Sigma-54 family (σ54), nitrogen regulation and alternative metabolism
6. rpoD (Q72B50): Sigma-70 family (σ70), housekeeping transcription

7. fliA (Q726C4): Sigma-28 family (σ28), flagellar gene expression

8. Over-annotation patterns:

9. Many sigma factors had GO:0003700 (DNA-binding transcription factor activity) which is incorrect - sigma factors recognize promoters but do not bind DNA themselves; the DNA-binding is performed by the RNAP core enzyme.
10. Proposed replacement with GO:0016987 (sigma factor activity).

Potassium Transport Pathway Reviews Completed:

Key findings from annotation reviews:

1. Two distinct K+ transport systems identified:
2. KdpFABC system (DVU3335-3338): High-affinity ATP-driven K+ pump induced under K+ limitation

3. Trk/Ktr system (DVU0412-0413, DVU1606): Constitutive K+ uptake channels

4. KdpFABC Complex - Functional assignments:

5. kdpB (Q725T7): P-type ATPase motor - the ONLY subunit with catalytic activity. Contains the catalytic aspartate D307 that cycles through phosphorylation. Annotated with GO:0008556 (P-type K+ transporter activity).
6. kdpC (Q725T8): Catalytic chaperone - does NOT have ATPase activity! Incorrectly annotated with ATP binding and hydrolase activity. Its actual function is GO:0001671 (ATPase activator activity) - it increases KdpB's ATP-binding affinity.
7. kdpD (Q725T9): Tandem serine-histidine kinase sensor that controls KdpFABC expression in response to K+ levels and turgor.

8. DVU3335 (Q725U0): KdpE-like response regulator partnered with KdpD for two-component signaling.

9. Trk/Ktr System - Pore vs Regulator distinction:

10. trkH (Q72F05): Membrane channel pore - this is the actual K+ transporter with transmembrane domains.
11. DVU0412 (Q72F06) and DVU1606 (Q72BM9): Cytosolic RCK (regulator of K+ conductance) regulatory subunits. These do NOT transport ions themselves - they form octameric gating rings that regulate the TrkH channel through ATP/ADP-dependent conformational changes.

12. Key correction: Both TrkA proteins were incorrectly annotated with GO:0008324 (transporter activity). They should have GO:0015459 (potassium channel regulator activity).

13. c-di-AMP signaling:

14. The second messenger c-di-AMP binds to RCK regulatory subunits to modulate K+ uptake capacity, linking potassium homeostasis to broader cellular signaling networks.

Slides

• Slides (Marp source: NITV2_PATHWAYS-slides.md) — AI generated