PMID:39078674

Identification and characterization of a small-molecule metallophore involved in lanthanide metabolism

mllG (META1p4136) belongs to DUF2218 and is present in the homologous rhodopetrobactin biosynthetic locus.

"META1p4136 (mllG) belongs to DUF2218 and is also present in the rhodopetrobactin locus"
The DUF2218 protein mllG is inferred to act in regulation or transport rather than in biosynthesis, based on the genomic context of its Vibrio cholerae homolog VCA0233 near iron-uptake regulation and xeno-siderophore uptake genes.

"suggesting DUF2218 is involved in regulation or transport rather than biosynthesis"
The mll locus (META1p4129-4138) is the most highly up-regulated gene set under poorly soluble Nd2O3, with an average 32-fold increase versus soluble NdCl3.

"the most highly up-regulated in the Nd2O3 condition, with an average increase in expression of 32-fold compared to growth with NdCl3"
The mll locus is homologous to NRPS-independent siderophore (NIS) biosynthetic gene clusters, but the product chelates lanthanides (it is a lanthanophore), not iron.

"is homologous to BGCs responsible for the transport, regulation, and biosynthesis of NRPS-independent siderophores"
The mll cluster produces a rhodopetrobactin-like lanthanophore.

"the cluster produces a rhodopetrobactin-like lanthanophore"
The methylolanthanin product binds the lanthanides lanthanum, neodymium, and lutetium.

"Methylolanthanin binds lanthanum (La), neodymium (Nd), and lutetium (Lu)"

file:METEA/mllG/mllG-deep-research-falcon.md

Falcon deep research report on mllG

The methylolanthanin literature identifies the mll locus (META1p4129-4138) and names META1p4136 as mllG, annotated as a DUF2218-family protein.

"identifies the **mll locus** in *M. extorquens* AM1 as **META1p4129–META1p4138** and names **META1p4136 as mllG**"
The AM1 methylolanthanin literature provides no enzymology supporting the UniProt-stated 2,4-dihydroxyhept-2-ene-1,7-dioic acid aldolase activity for mllG.

"does **not** provide enzymology (reaction, substrates, kinetics) supporting that specific aldolase activity for **mllG/META1p4136**"
Comparative genomics suggests DUF2218 proteins such as mllG act in regulation or transport rather than core biosynthesis chemistry.

"DUF2218 proteins are involved in **regulation or transport** rather than core biosynthesis chemistry"
Methylolanthanin is the first reported biological lanthanide chelator (lanthanophore) and carries a distinctive 4-hydroxybenzoate motif.

"the **first reported biological lanthanide chelator/lanthanophore**, with a distinctive **4-hydroxybenzoate** motif"
The mll locus is induced on average ~32-fold under growth with poorly soluble Nd2O3.

"with an average reported induction of **~32-fold**"
Methylolanthanin forms detectable complexes with multiple lanthanides, including La(III), Nd(III), and Lu(III).

"complexes with multiple lanthanides, including **La(III), Nd(III), and Lu(III)**"
The bottom-line annotation is that mllG is an uncharacterized DUF2218 family protein in the methylolanthanin lanthanophore locus, probably contributing accessory transport/regulation/accessory steps in lanthanide acquisition.

"the strongest current evidence supports annotation as an **uncharacterized DUF2218 family protein in the methylolanthanin lanthanophore locus**, probably contributing to **transport/regulation/accessory steps in lanthanide acquisition**"

file:METEA/mllG/mllG-deep-research-perplexity.md

Deep research report on mllG from Perplexity AI

mllG is predicted to have regulatory or transport functions rather than direct biosynthetic activities.

"predicted to have regulatory or transport functions rather than direct biosynthetic activities"
The Vibrio cholerae homolog VCA0233 lies adjacent to iron-uptake regulators and xeno-siderophore uptake genes, suggesting mllG may function in regulation or transport rather than biosynthesis.

"may be involved in regulation or transport rather than biosynthesis"
mllG belongs to the DUF2218 family.

"It belongs to DUF2218 family"
The available evidence for annotation relies on its location within a metallophore biosynthetic cluster.

"its location within a metallophore biosynthetic cluster"