| Claim/feature | Evidence summary (1–2 sentences) | Key genes/pathways | Quantitative details | Source (author-year, journal) | URL | Publication date | Citation ID |
|---|---|---|---|---|---|---|---|
| Identity: MxbM is the response regulator in the MOX cluster adjacent to mxbD | A genomic review of *Methylobacterium/Methylorubrum extorquens* AM1 annotates **mxbM** (historically **moxM**) as a transcriptional regulator in methylotrophy cluster 2, with neighboring **mxbD/moxD** annotated as a sensor kinase, consistent with a two-component sensor-regulator pair. This matches UniProt C5B132 as a two-component transcriptional regulator in AM1. (pqac-00000001) | **mxbM/moxM**, **mxbD/moxD**; MOX cluster; methanol oxidation locus | No quantitative values reported in the excerpt | Chistoserdova et al. 2003, *Journal of Bacteriology* | https://doi.org/10.1128/jb.185.10.2980-2987.2003 | May 2003 | (pqac-00000001) |
| Functional role: required for activation of the **mxa** operon and repression of **xox1** | Review evidence summarizing experimental genetics in AM1 states that **MxcE, MxaB, and MxbM are required for mxa operon expression**, whereas **MxbM is specifically required for repression of the xox1 operon**. Independent review/excerpted summaries also describe MxbDM as increasing **mxa** expression while decreasing **xoxF/xox1** expression. (pqac-00000000, pqac-00000004, pqac-00000006) | **mxa** operon (**mxaFI**), **xox1/xoxF** operon; methanol dehydrogenase expression control | No MxbM-specific fold changes reported in retrieved excerpts | Skovran et al. 2019, *Current Issues in Molecular Biology*; summarized in Chu & Lidstrom 2016, *Journal of Bacteriology* | https://doi.org/10.21775/cimb.033.101; https://doi.org/10.1128/jb.00959-15 | Jan 2019; Apr 2016 | (pqac-00000000, pqac-00000004, pqac-00000006) |
| Lanthanide-switch involvement and apo-XoxF signaling model | In AM1, lanthanide-responsive reporter studies support a model in which **apo-XoxF** functions as a lanthanide sensor: in the absence of lanthanides it activates **mxa** and represses **xox1** via **MxcQE/MxbDM**, while lanthanide-bound XoxF no longer drives that regulatory state. The same study notes that expression from **mxa** and **xox1** promoters is highly sensitive to La, Ce, Pr, and Nd. (pqac-00000005, pqac-00000007) | **xoxF1**, **mxa**, **xox1**, **MxcQE**, **MxbDM**; lanthanide switch | Reporter assays used **20 μM Ca** and lanthanides from **2.5 nM to 20 μM**; specific lanthanide tests included **2 μM** lanthanides and **20 μM Sm**; promoterless Venus background **58 ± 5 RFU/OD600**; purified XoxF dimer contained **1.24 La atoms** and no Ca. (pqac-00000005, pqac-00000007) | Vu et al. 2016, *Journal of Bacteriology* | https://doi.org/10.1128/jb.00937-15 | Apr 2016 | (pqac-00000005, pqac-00000007) |
| Regulatory cascade hypothesis: **MxcQE → mxbDM** | A regulatory cascade has been proposed in which **MxcQE activates mxbDM**, placing MxbM downstream of another two-component system in the methanol dehydrogenase regulatory network. This remains a model-level interpretation rather than a fully biochemically resolved pathway. (pqac-00000000, pqac-00000006) | **MxcQE**, **mxbDM**, **mxa**, **xox1** | No direct quantitative cascade measurements reported in retrieved excerpts | Skovran et al. 2019, *Current Issues in Molecular Biology* | https://doi.org/10.21775/cimb.033.101 | Jan 2019 | (pqac-00000000, pqac-00000006) |
| Unresolved mechanism: phosphorylation state and direct DNA binding not shown | Reviews emphasize that although genetic evidence supports MxbM function, the **phosphorylation state of the regulators and direct DNA binding have not been demonstrated**. Thus, MxbM is strongly inferred to be a DNA-binding response regulator from genetics/domain architecture, but the direct molecular mechanism remains unresolved. (pqac-00000000, pqac-00000006, pqac-00000008) | Response-regulator signaling; transcriptional control of **mxa/xox1** | No biochemical constants or phosphosite data reported in retrieved excerpts | Skovran et al. 2019, *Current Issues in Molecular Biology* | https://doi.org/10.21775/cimb.033.101 | Jan 2019 | (pqac-00000000, pqac-00000006, pqac-00000008) |
| Lanthanide-dependent growth context relevant to MxbM-regulated methanol oxidation | Review data for AM1 show that lanthanides strongly enhance methylotrophic growth conditions in which the **mxa/xox** switch operates, providing physiological context for the MxbM-controlled network. These data are not MxbM-specific mutant measurements but are relevant to the pathway MxbM regulates. (pqac-00000011) | Lanthanide-dependent methanol oxidation; **mxaFI/xoxF** systems | AM1 reached **OD600 = 1.6** in culture tubes with **100 nM La**; optimal growth rate and density were reported at **1 μM La**. Environmental REE levels were noted as pico- to nanomolar, with low micromolar soluble REE in some acidic settings. (pqac-00000011) | Skovran et al. 2019, *Current Issues in Molecular Biology* | https://doi.org/10.21775/cimb.033.101 | Jan 2019 | (pqac-00000011) |
| Application: methanol biosensor using the **mxbDM** sensor domain | A synthetic biology study engineered the **methanol-sensing domain of MxbD** from *M. extorquens* into chimeric histidine kinases in *E. coli*, demonstrating practical reuse of the AM1 methanol-responsive regulatory system. While the engineered construct used MxbD rather than MxbM directly, it exploits the same native regulatory module historically linked to **mxbDM/mxcQE/mxaB** control of methanol oxidation genes. (pqac-00000012, pqac-00000015) | **mxbDM**, **mxcQE**, **mxaB**; methanol sensing; engineered two-component signaling | Maximum fluorescence at **0.05% methanol** for **MxbDZ** and **0.01% methanol** for **MxcQZ**; both detected as low as **0.01% methanol**; maximal sensor-kinase expression at **0.5 mM IPTG**; max **ompC** expression at **2% methanol** for MxbDZ and **0.01%** for MxcQZ; correlation coefficient **0.94592**; allowable environmental limit cited as **200 ppm (0.02%)**; global methanol production context **~100 million metric tons/year** across **>90 plants**. (pqac-00000012, pqac-00000015) | Selvamani et al. 2020, *J. Microbiol. Biotechnol.* / DOI record | https://doi.org/10.4014/mbl.1908.08009 | Mar 2020 | (pqac-00000012, pqac-00000015) |
| Recent 2023 link: MxbDM-regulated methylotaxis and plant colonization | In *Methylobacterium aquaticum* 22A, a 2023 study reports that methylotaxis sensor **MtpC** is regulated under **MxbDM**, which is also required for **MxaF** expression. This is not AM1-specific or MxbM-specific biochemistry, but it is recent comparative evidence that the MxbDM module can couple methanol oxidation regulation to plant-associated behavior. (pqac-00000009) | **MxbDM**, **MxaFI**, **XoxF**, **MtpC**; methylotaxis; plant colonization | Triple MCP mutant lost methylotaxis and showed slower gathering to plant tissues and reduced colonization, but the excerpt gives no numeric effect sizes for MxbDM specifically. (pqac-00000009) | Tani et al. 2023, *Frontiers in Microbiology* | https://doi.org/10.3389/fmicb.2023.1258452 | Oct 2023 | (pqac-00000009) |
| Lanthanide uptake/storage findings relevant to applications of the regulated pathway | Work on AM1 lanthanide homeostasis identified a **TonB-ABC transport system** required for lanthanide uptake, repression of the TonB receptor by excess lanthanides, and **cytoplasmic lanthanide storage inclusions** visualized by TEM/EDS. These findings are relevant to applications such as lanthanide biorecovery and to understanding the upstream metal availability that drives the MxbM-linked methanol oxidation switch. (pqac-00000010) | **xoxF1**, lanthanide transport cluster (**lut** context), TonB-ABC transport; lanthanide storage | Lanthanides were shown as cytoplasmic inclusions by TEM/EDS; no explicit concentration/performance numbers for biorecovery were reported in the excerpt. (pqac-00000010) | Roszczenko-Jasińska et al. 2020, *Scientific Reports* | https://doi.org/10.1038/s41598-020-69401-4 | Jul 2020 | (pqac-00000010) |


*Table: This table summarizes the strongest available evidence for the identity, function, regulatory context, and applied relevance of MxbM/MxbDM in Methylorubrum extorquens AM1. It distinguishes experimentally supported claims from unresolved mechanistic inferences and includes quantitative details where present.*