The mll lanthanophore cluster

Re-annotating an "iron-siderophore" system in Methylorubrum extorquens AM1 as lanthanide acquisition

AI Gene Review · projects/METEA_MLL_CLUSTER · 2026

Bottom line

  • The mll cluster makes and imports methylolanthanin, a lanthanide chelator that feeds the XoxF methanol dehydrogenase.
  • Databases call it iron-siderophore machinery (homology to aerobactin and petrobactin genes). We reviewed all 10 genes to replace that story.
  • 31 rows: iron-transport rows on MluA removed or generalised, 8 NEW rows for genes with little or no GOA; GO has no lanthanophore term, so one is proposed.

How the system works

Why it was misannotated

Feature Iron siderophores Methylolanthanin
Metal Fe³⁺ La³⁺, Ce³⁺, Nd³⁺ ...
Induced by iron limitation lanthanide limitation (~32-fold)
Enzyme families IucA/IucC, AsbD/AsbE MllA (IucA-like), MllBC (AsbD/E-like)
Receptor FepA, FpvA (TonB) MluA (TonB)
Regulation Fur MluI / MluR (ECF σ / anti-σ)

Homology to the iron enzymes is real; the substrate and product are not iron.

Correcting MluA

mluA review: iron ion transport removed; siderophore-iron transmembrane transporter activity generalised to transmembrane transporter activity.

What changed across 10 genes

Action Rows Where
ACCEPT 8 acid-amino acid ligase (MllA, MllBC), outer membrane, sigma / anti-sigma
KEEP_AS_NON_CORE 7 e.g. MllA siderophore biosynthesis (analogous chemistry)
NEW 8 mllDE, mllF, mllJ had no GOA; one on mllH
REMOVE 4 3 iron rows on MluA; wrong EC ligase on MllBC
MODIFY 3 2 iron-transporter MF on MluA; MllH acyltransferase
MARK_AS_OVER_ANNOTATED 1 MluI generic TF activity

mllG has no GOA and no molecular function asserted: DUF2218, and the only name is a machine prediction.

Status and next steps

  • ✅ 10/10 reviews exist; deep research from Perplexity and Falcon for each gene.
  • ⬜ Review files are DRAFT or INITIALIZED except mllDE; the project page's action table and several UniProt IDs are out of date.
  • ⬜ Propose lanthanophore biosynthetic process and a lanthanide-metallophore transport term to GO.

Read more: projects/METEA_MLL_CLUSTER.md · genes/METEA/mll*/ · genes/METEA/mlu*/ · related: projects/REE.md