Function
Incorporates a malonate or methylmalonate polyketide unit onto the N-acyl-arginine starter unit (loaded upstream on Var3 / ALG65336.1) and reduces the beta-keto group via its KS-AT-KR-ACP module.
A conserved hybrid polyketide synthase / nonribosomal peptide synthetase (PKS/NRPS) biosynthetic and iron-transport module (the var gene cluster) in soil and rhizosphere Variovorax species (exemplified by Variovorax paradoxus P4B GenBank KT362218 producing variobactin A/B, and Variovorax boronicumulans and Variovorax sp. H002 producing variochelins A-E). Downstream of the unreviewed starter NRPS Var3 (ALG65336.1, loading the N-acyl-arginine starter unit), the cytoplasmic hybrid PKS/NRPS/TauD megasynthase Var4 (VarG) extends the N-acyl-arginine starter with a malonate/methylmalonate ketide unit, reduces the beta-keto group, condenses the ketide-extended intermediate with the position-3 aspartate monomer loaded in trans on Var5 (ALG65340.1), and beta-hydroxylates that aspartate residue via its C-terminal TauD domain to install the photoreactive beta-hydroxyaspartate (Hya; reported as L-erythro-Hya for TauD-type hydroxylases in PMID:38590537, though L-threo-Hya was earlier reported for variochelin A in PMID:27023373) ligand; the bimodular NRPS Var6 elongates and epimerizes two internal peptide monomers (established as D-Ser and L-Pro in Variovorax sp. H002 variochelins in PMID:38590537, with Ser/Thr combinatorialization and amino-acid substitutions noted in V. paradoxus P4B variobactin A/B in PMID:26412281); and the terminal bimodular NRPS-thioesterase Var7 incorporates two C-terminal modified N-hydroxyornithine hydroxamate chelators (established as N-delta-acetyl-N-delta-hydroxy-L-ornithine in H002 variochelins and combinatorialized across N-formyl/N-acetyl/unmodified N-hydroxyornithine in P4B variobactin) and cleaves the mature lipopeptide siderophore. The inner-membrane SyrD-family type I ABC half-transporter Var14 exports the apo-siderophore across the cytoplasmic membrane. After extracellular Fe(III) chelation (and optional light-driven Fe(III)-to-Fe(II) photolysis), the outer-membrane TonB-dependent receptor Var8 imports ferric-variobactin/variochelin across the outer membrane, and following uptake into the cytoplasm, the FhuF-family ferric-siderophore reductase Var13 reduces complexed Fe(III) to release bioavailable Fe(II).
All recommended fields populated.
✗ none found
No MODULE:variochelin_siderophore_biosynthesis_and_uptake deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
9 gene-function check(s) reflected in core functions · 0 conflict(s) · 9 evidence or coverage gap(s) (18 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| var4_acyltransferase_activity | var4 (Variovorax paradoxus P4B) UniProtKB:A0A0N7FMV9 Family Representative |
polyketide synthase activity GO:0016218 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var4_nrps_condensation_activity | var4 (Variovorax paradoxus P4B) UniProtKB:A0A0N7FMV9 Family Representative |
non-ribosomal peptide synthetase activity GO:1904091 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var4_taud_dioxygenase_activity | var4 (Variovorax paradoxus P4B) UniProtKB:A0A0N7FMV9 Family Representative |
2-oxoglutarate-dependent dioxygenase activity GO:0016706 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var6_ligase_activity | var6 (Variovorax paradoxus P4B) UniProtKB:A0A0N9LX43 Family Representative |
non-ribosomal peptide synthetase activity GO:1904091 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var7_ligase_activity | var7 (Variovorax paradoxus P4B) UniProtKB:A0A0N9LYB5 Family Representative |
non-ribosomal peptide synthetase activity GO:1904091 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var7_thioesterase_activity | var7 (Variovorax paradoxus P4B) UniProtKB:A0A0N9LYB5 Family Representative |
thiolester hydrolase activity GO:0016790 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var14_abc_exporter_activity | var14 (Variovorax paradoxus P4B) UniProtKB:A0A0N9LS79 Family Representative |
ABC-type transporter activity GO:0140359 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var8_receptor_transporter_activity | var8 (Variovorax paradoxus P4B) UniProtKB:A0A0N9M610 Family Representative |
siderophore uptake transmembrane transporter activity GO:0015344 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var13_reductase_activity | var13 (Variovorax paradoxus P4B) UniProtKB:A0A0N9M354 Family Representative |
ferric-chelate reductase activity GO:0000293 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| var4_acyltransferase_activity | Var4/VarG hybrid PKS/NRPS/TauD siderophore megasynthases Family |
polyketide synthase activity GO:0016218 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var4_nrps_condensation_activity | Var4/VarG hybrid PKS/NRPS/TauD siderophore megasynthases Family |
non-ribosomal peptide synthetase activity GO:1904091 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var4_taud_dioxygenase_activity | Var4/VarG hybrid PKS/NRPS/TauD siderophore megasynthases Family |
2-oxoglutarate-dependent dioxygenase activity GO:0016706 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var6_ligase_activity | Var6 bimodular variobactin/variochelin NRPS elongases Family |
non-ribosomal peptide synthetase activity GO:1904091 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var7_ligase_activity | Var7 terminal variobactin/variochelin NRPS-thioesterases Family |
non-ribosomal peptide synthetase activity GO:1904091 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var7_thioesterase_activity | Var7 terminal variobactin/variochelin NRPS-thioesterases Family |
thiolester hydrolase activity GO:0016790 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var14_abc_exporter_activity | Var14 SyrD-family lipopeptide siderophore ABC exporters Family |
ABC-type transporter activity GO:0140359 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var8_receptor_transporter_activity | Var8 TonB-dependent ferric-variobactin/variochelin receptors Family |
siderophore uptake transmembrane transporter activity GO:0015344 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| var13_reductase_activity | Var13 FhuF-family ferric-siderophore reductases Family |
ferric-chelate reductase activity GO:0000293 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
6 complete review(s) · 0 with deep research · 0 missing review · 6 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| var13 A0A0N9M354 | ✓ | ✓ | ✗ |
| var14 A0A0N9LS79 | ✓ | ✓ | ✗ |
| var4 A0A0N7FMV9 | ✓ | ✓ | ✗ |
| var6 A0A0N9LX43 | ✓ | ✓ | ✗ |
| var7 A0A0N9LYB5 | ✓ | ✓ | ✗ |
| var8 A0A0N9M610 | ✓ | ✓ | ✗ |
Grounded on the six GOA-annotated proteins of the Variovorax paradoxus strain P4B (NCBITaxon:34073) variobactin gene cluster (GenBank KT362218.1, 41,899 bp, var1-var14; PMID:26412281) — A0A0N7FMV9 (Var4, ALG65339.1), A0A0N9LX43 (Var6, ALG65341.1), A0A0N9LYB5 (Var7, ALG65342.1), A0A0N9M610 (Var8, ALG65343.1), A0A0N9M354 (Var13, ALG65348.1), and A0A0N9LS79 (Var14, ALG65349.1) — together with comparative characterization and varG::cmR knockout validation of the orthologous variochelin var gene clusters in Variovorax boronicumulans (PMID:27023373) and Variovorax sp. H002 (PMID:38590537). Note that GenBank KT362218.1 assigns protein_id accessions non-monotonically across the first three ORFs (verified in var4-bioinformatics/KT362218_features.gb and RESULTS.md), followed in locus order by var4-var14 (ALG65339.1-ALG65349.1). Remaining ORFs in GenBank KT362218.1 lacking UniProt GOA records account for the upstream starter and intervening assembly-line steps: var1 (1..834, ALG65337.1, GenBank note "thioesterase", type II editing thioesterase), var2 (812..1513, ALG65338.1, GenBank note "phospantetheinyl transferase", 4'-phosphopantetheinyl transferase), var3 (1510..6735, ALG65336.1, GenBank note "nonribosomal peptide synthetase", starter NRPS loading the N-terminal fatty-acyl and L-arginine units upstream of Var4), var5 (13769..16882, ALG65340.1, GenBank note "nonribosomal peptide synthetase", intervening NRPS module between var4 and var6 that activates and tethers the position-3 aspartate monomer in trans for Var4's LCL condensation and TauD beta-hydroxylase domains), var9/var10 (complement(34707..35735) / complement(35732..36310), ALG65344.1/ALG65345.1, FecR-like anti-sigma factor and ECF sigma-24 subunit paired with Var8's STN domain), and var11/var12 (complement(36472..37791) / complement(37778..38884), ALG65346.1/ALG65347.1, GenBank notes "lysine N-monooxygenase" and "n-acetyltransferase", supplying the N-hydroxylated and N-acylated ornithine substrates of Var7). Similarly, the inner-membrane transporter mediating periplasm-to-cytoplasm import of ferric-variobactin between outer-membrane Var8 and cytoplasmic Var13 is uncharacterized and recorded as KNOWLEDGE_GAP.
Incorporates a malonate or methylmalonate polyketide unit onto the N-acyl-arginine starter unit (loaded upstream on Var3 / ALG65336.1) and reduces the beta-keto group via its KS-AT-KR-ACP module.
Condenses the polyketide-extended 4-acylamino-7-guanidino-3-hydroxy-2-methylheptanoyl-S-ACP intermediate with the position-3 aspartate monomer loaded in trans on Var5 (ALG65340.1) to form the Var5-tethered lipodipeptidyl-S-PCP intermediate (note that whether TauD beta-hydroxylation occurs after or prior to LCL condensation on Var5-tethered Asp remains experimentally open).
Catalyzes Fe(II)/2-oxoglutarate-dependent beta-hydroxylation of the Var5-tethered position-3 aspartate residue (modeled sequentially on L-aspartyl-containing lipodipeptidyl-S-PCP, though hydroxylation of L-aspartyl-S-PCP prior to LCL condensation is also mechanistically plausible) to install the photoreactive beta-hydroxyaspartate iron-coordinating ligand.
Activates, condenses, and epimerizes two internal peptide monomers (established as L-Ser epimerized to D-Ser and L-Pro in Variovorax sp. H002 variochelins, PMID:38590537, with Ser/Thr interchange and amino-acid substitutions noted in V. paradoxus P4B variobactin A/B, PMID:26412281) onto the growing lipopeptidyl-S-PCP intermediate.
Activates and condenses the two C-terminal modified N-hydroxyornithine residues (established as N-delta-acetyl-N-delta-hydroxy-L-ornithine in H002 variochelins, PMID:38590537, and combinatorialized across N-formylated, N-acetylated, or unmodified N-hydroxyornithine in P4B variobactin, PMID:26412281) that form the bidentate hydroxamate iron-binding ligands.
Hydrolyzes the full-length lipohexapeptidyl-S-PCP thioester to release the mature apo-siderophore variobactin into the cytoplasm.
Couples ATP hydrolysis to the export of newly synthesized apo-variobactin across the cytoplasmic membrane.
Recognizes extracellular ferric-variobactin complexes and mediates TonB-dependent import across the bacterial cell outer membrane.
Catalyzes one-electron reduction of Fe(III) bound to imported variobactin, releasing bioavailable Fe(II) for cellular incorporation.