ID TMM_METSB Reviewed; 451 AA. AC B8EIZ7; DT 28-JUN-2023, integrated into UniProtKB/Swiss-Prot. DT 03-MAR-2009, sequence version 1. DT 24-JUL-2024, entry version 64. DE RecName: Full=Trimethylamine monooxygenase {ECO:0000303|PubMed:22006322}; DE Short=TMA monooxygenase {ECO:0000303|PubMed:22006322}; DE Short=Tmm {ECO:0000303|PubMed:22006322}; DE EC=1.14.13.148 {ECO:0000269|PubMed:22006322}; GN Name=tmm {ECO:0000303|PubMed:22006322}; GN OrderedLocusNames=Msil_3604 {ECO:0000312|EMBL:ACK52489.1}; OS Methylocella silvestris (strain DSM 15510 / CIP 108128 / LMG 27833 / NCIMB OS 13906 / BL2). OC Bacteria; Pseudomonadota; Alphaproteobacteria; Hyphomicrobiales; OC Beijerinckiaceae; Methylocella. OX NCBI_TaxID=395965; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=DSM 15510 / CIP 108128 / LMG 27833 / NCIMB 13906 / BL2; RX PubMed=20472789; DOI=10.1128/jb.00506-10; RA Chen Y., Crombie A., Rahman M.T., Dedysh S.N., Liesack W., Stott M.B., RA Alam M., Theisen A.R., Murrell J.C., Dunfield P.F.; RT "Complete genome sequence of the aerobic facultative methanotroph RT Methylocella silvestris BL2."; RL J. Bacteriol. 192:3840-3841(2010). RN [2] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INDUCTION, AND RP DISRUPTION PHENOTYPE. RC STRAIN=DSM 15510 / CIP 108128 / LMG 27833 / NCIMB 13906 / BL2; RX PubMed=22006322; DOI=10.1073/pnas.1112928108; RA Chen Y., Patel N.A., Crombie A., Scrivens J.H., Murrell J.C.; RT "Bacterial flavin-containing monooxygenase is trimethylamine RT monooxygenase."; RL Proc. Natl. Acad. Sci. U.S.A. 108:17791-17796(2011). CC -!- FUNCTION: Catalyzes the oxidation of trimethylamine (TMA) to produce CC trimethylamine N-oxide (TMAO) (PubMed:22006322). In vitro, has a broad CC substrate specificity, oxidizing many nitrogen- and sulfur-containing CC compounds, including dimethylamine (DMA), dimethylsulfide (DMS), CC dimethylsulfoxide (DMSO), cysteamine, methimazole and dimethylaniline CC (PubMed:22006322). {ECO:0000269|PubMed:22006322}. CC -!- CATALYTIC ACTIVITY: CC Reaction=NADPH + O2 + trimethylamine = H2O + NADP(+) + trimethylamine CC N-oxide; Xref=Rhea:RHEA:31979, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:15724, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, CC ChEBI:CHEBI:58389; EC=1.14.13.148; CC Evidence={ECO:0000269|PubMed:22006322}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31980; CC Evidence={ECO:0000269|PubMed:22006322}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:A3SLM3}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=9.4 uM for TMA {ECO:0000269|PubMed:22006322}; CC KM=89.7 uM for DMA {ECO:0000269|PubMed:22006322}; CC KM=10.3 uM for DMS {ECO:0000269|PubMed:22006322}; CC KM=3575 uM for DMSO {ECO:0000269|PubMed:22006322}; CC KM=3139 uM for cysteamine {ECO:0000269|PubMed:22006322}; CC KM=28.2 uM for methimazole {ECO:0000269|PubMed:22006322}; CC KM=35.7 uM for dimethylaniline {ECO:0000269|PubMed:22006322}; CC Vmax=29.4 nmol/min/mg enzyme with TMA as substrate CC {ECO:0000269|PubMed:22006322}; CC Vmax=6.9 nmol/min/mg enzyme with DMA as substrate CC {ECO:0000269|PubMed:22006322}; CC Vmax=34.6 nmol/min/mg enzyme with DMS as substrate CC {ECO:0000269|PubMed:22006322}; CC Vmax=4.8 nmol/min/mg enzyme with DMSO as substrate CC {ECO:0000269|PubMed:22006322}; CC Vmax=76.2 nmol/min/mg enzyme with cysteamine as substrate CC {ECO:0000269|PubMed:22006322}; CC Vmax=14.4 nmol/min/mg enzyme with methimazole as substrate CC {ECO:0000269|PubMed:22006322}; CC Vmax=29.2 nmol/min/mg enzyme with dimethylaniline as substrate CC {ECO:0000269|PubMed:22006322}; CC -!- INDUCTION: Expression is induced by TMA. {ECO:0000269|PubMed:22006322}. CC -!- DISRUPTION PHENOTYPE: Mutant cannot grow on TMA as a sole source of CC carbon and energy. {ECO:0000269|PubMed:22006322}. CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP001280; ACK52489.1; -; Genomic_DNA. DR RefSeq; WP_012592557.1; NC_011666.1. DR AlphaFoldDB; B8EIZ7; -. DR SMR; B8EIZ7; -. DR STRING; 395965.Msil_3604; -. DR KEGG; msl:Msil_3604; -. DR eggNOG; COG2072; Bacteria. DR HOGENOM; CLU_006909_3_0_5; -. DR OrthoDB; 324612at2; -. DR Proteomes; UP000002257; Chromosome. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro. DR GO; GO:0047822; F:hypotaurine dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IEA:UniProtKB-EC. DR GO; GO:0050661; F:NADP binding; IEA:InterPro. DR GO; GO:0034899; F:trimethylamine monooxygenase activity; IEA:RHEA. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR InterPro; IPR000960; Flavin_mOase. DR InterPro; IPR020946; Flavin_mOase-like. DR InterPro; IPR050346; FMO. DR PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1. DR PANTHER; PTHR23023:SF301; FLAVIN-CONTAINING MONOOXYGENASE; 1. DR Pfam; PF00743; FMO-like; 2. DR PIRSF; PIRSF000332; FMO; 1. DR PRINTS; PR00411; PNDRDTASEI. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 2. PE 1: Evidence at protein level; KW FAD; Flavoprotein; Monooxygenase; NADP; Oxidoreductase; Reference proteome. FT CHAIN 1..451 FT /note="Trimethylamine monooxygenase" FT /id="PRO_0000458075" FT BINDING 12 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 37 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 39 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 45 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 46 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 62 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 70 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 72 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 72 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 125 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 204 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 205 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 207 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 228 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 317 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 320 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" FT BINDING 411 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:A3SLM3" SQ SEQUENCE 451 AA; 51699 MW; E4856E54189574A3 CRC64; MTRVAIIGAG PSGLAQLRAF QSAGKKGAAI PELVCFEKQS DWGGLWNYTW RTGVDEYGEP VHGSMYRYLW SNGPKECLEF ADYSFEEHFG RPIPSYPPRA VLHDYIMGRV EKSDVRKFVR FSTVVRWIDF DETTQLFTVT VKDLKKDELY SETFDYVVVA SGHFSTPNVP HFPGIEVFPG RVLHAHDFRD ANEFVGKNLL VVGSSYSAED IASQCYKYGA KSITFSYRSK PLNFDWPECF TVKPLLTKLT GKTAHFKDGS EAVVDAVLLC TGYLHHFPFL ADNLRLKTNN RLYPAGLYKG IFWQDNPKLI YLGMQDQYFT FNMFDAQAWY ARDVILGRIK LPAAEERQAD IDHWRGLEEK LETAFDGIDF QTEYMRDLIP ATDYPMFDLD KVAALFKEWE EDKVKSIMGY RDNSYVSIMT GNKAPPHHTK WMEALDDSFD AFQNRPEAAA E //