| Gene/protein | Verified identity | Reaction catalyzed | Substrates / cofactors | Pathway / module | Key genetic evidence in *Methylorubrum extorquens* AM1 | Recent 2024 evidence / broader relevance | Localization / compartment | Key references |
|---|---|---|---|---|---|---|---|---|
| **fae**; UniProt **Q9FA38**; locus **META1p1766 / MexAM1_META1p1766** | Matches the canonical **formaldehyde-activating enzyme (Fae)** annotation in *M. extorquens* AM1; reviews/tables place **fae/META1p1766** in the H4MPT-dependent C1 transfer module as a formaldehyde-activating enzyme (pqac-00000004) | Catalyzes/strongly accelerates condensation of **formaldehyde + tetrahydromethanopterin (H4MPT)** to form **methylene-H4MPT**, the entry step into the H4MPT-linked oxidation route; spontaneous condensation can occur, but Fae is the physiologically important catalyst (pqac-00000000, pqac-00000005) | **Formaldehyde** is the C1 substrate and **H4MPT** is the C1 carrier/cofactor acceptor; product is **methylene-H4MPT** feeding downstream H4MPT enzymes (pqac-00000000, pqac-00000005) | Central entry enzyme of the **H4MPT-linked formaldehyde oxidation/detoxification pathway**, the primary route for formaldehyde oxidation in AM1 during methylotrophic growth; pathway converts toxic intracellular formaldehyde toward formate/CO2 via downstream H4MPT enzymes (pqac-00000000, pqac-00000002, pqac-00000006) | **fae null mutants cannot grow on methanol** and are **methanol/formaldehyde sensitive during growth on succinate**, supporting a formaldehyde detoxification role. In plate assays, all tested H4MPT-pathway mutants were unable to grow on methanol; **1 mM methanol** inhibited pathway mutants and **125 mM methanol** abolished growth of tested mutants in succinate-based assays (pqac-00000002, pqac-00000006) | In 2024, glycine betaine catabolism in *M. extorquens* PA1 was shown to generate free formaldehyde that must be processed by methylotrophy machinery; a **dgcB^P30L Δfae** strain showed **no growth (NG)** on glycine betaine, linking Fae-dependent H4MPT chemistry to detoxification/energy capture from non-methanol substrates that release formaldehyde (pqac-00000008, pqac-00000009, pqac-00000014) | Evidence places the reaction in the **cytoplasm / intracellular soluble compartment**, because formaldehyde entering the cytoplasm condenses with H4MPT and the H4MPT pathway is described as the intracellular primary oxidation/detoxification route; no evidence for secretion or membrane localization was identified here (pqac-00000000) | Marx et al., **2003**, *J. Bacteriol.* DOI: https://doi.org/10.1128/jb.185.23.7160-7168.2003 (pqac-00000000, pqac-00000002, pqac-00000006); Nayak & Marx, **2014**, *PLoS ONE* DOI: https://doi.org/10.1371/journal.pone.0107887 (pqac-00000005); Ochsner et al., **2015**, *Appl. Microbiol. Biotechnol.* DOI: https://doi.org/10.1007/s00253-014-6240-3 (pqac-00000003, pqac-00000004); Hying et al., **2024**, *Appl. Environ. Microbiol.* DOI: https://doi.org/10.1128/aem.02090-23 (pqac-00000008, pqac-00000009, pqac-00000014) |


*Table: This table summarizes the verified identity, catalytic role, pathway placement, localization, and key genetic evidence for *Methylorubrum extorquens* AM1 Fae (Q9FA38). It also includes recent 2024 evidence linking Fae-dependent formaldehyde handling to glycine betaine metabolism.*