Rhea - reaction knowledgebase

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Name ^help_outline AH₂ Identifier CHEBI:17499 Charge 0 Formula RH2 SMILES^help_outline *([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 2,799 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} Identifier CHEBI:142876 Charge -2 Formula C11H17N3O11P2 InChIKey^help_outline ODFOOQGQRDVSPW-PEBGCTIMSA-L SMILES^help_outline O(P(=O)([O-])OC[C@H]1O[C@@H](N2C=CC(=NC2=O)N)[C@@H]([C@@H]1O)O)P(=O)([O-])CCO 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline S-adenosyl-L-methionine Identifier CHEBI:59789 Charge 1 Formula C15H23N6O5S InChIKey^help_outline MEFKEPWMEQBLKI-AIRLBKTGSA-O SMILES^help_outline C[S+](CC[C@H]([NH3+])C([O-])=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 868 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline 5'-deoxyadenosine Identifier CHEBI:17319 (CAS: 4754-39-6) ^help_outline Charge 0 Formula C10H13N5O3 InChIKey^help_outline XGYIMTFOTBMPFP-KQYNXXCUSA-N SMILES^help_outline C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 69 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline A Identifier CHEBI:13193 Charge Formula R SMILES^help_outline * 2D coordinates Mol file for the small molecule Search links Involved in 2,870 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate) Identifier CHEBI:142877 Charge -2 Formula C12H19N3O11P2 InChIKey^help_outline VQDRQBLAARRQFV-CNYIRLTGSA-L SMILES^help_outline O(P(=O)([O-])OC[C@H]1O[C@@H](N2C=CC(=NC2=O)N)[C@@H]([C@@H]1O)O)P(=O)([O-])C[C@H](C)O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline H⁺ Identifier CHEBI:15378 Charge 1 Formula H InChIKey^help_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILES^help_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline L-methionine Identifier CHEBI:57844 Charge 0 Formula C5H11NO2S InChIKey^help_outline FFEARJCKVFRZRR-BYPYZUCNSA-N SMILES^help_outline CSCC[C@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 121 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline S-adenosyl-L-homocysteine Identifier CHEBI:57856 Charge 0 Formula C14H20N6O5S InChIKey^help_outline ZJUKTBDSGOFHSH-WFMPWKQPSA-N SMILES^help_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](CSCC[C@H]([NH3+])C([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 792 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:59072	RHEA:59073	RHEA:59074	RHEA:59075
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	1 proteins	1 proteins
EC numbers ^help_outline	2.1.1.308
MetaCyc ^help_outline		RXN-9010

Publications

A (re)discovery of the Fom3 substrate.

Blaszczyk A.J., Booker S.J.

Biochemistry 57:891-892(2018) [PubMed] [EuropePMC]
Methylcobalamin-dependent radical SAM C-methyltransferase Fom3 recognizes cytidylyl-2-hydroxyethylphosphonate and catalyzes the nonstereoselective C-methylation in fosfomycin biosynthesis.

Sato S., Kudo F., Kim S.Y., Kuzuyama T., Eguchi T.

A methylcobalamin (MeCbl)-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase Fom3 was found to catalyze the C-methylation of cytidylyl-2-hydroxyethylphosphonate (HEP-CMP) to give cytidylyl-2-hydroxypropylphosphonate (HPP-CMP), although it was originally proposed to catalyze the C-me ... >> More

A methylcobalamin (MeCbl)-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase Fom3 was found to catalyze the C-methylation of cytidylyl-2-hydroxyethylphosphonate (HEP-CMP) to give cytidylyl-2-hydroxypropylphosphonate (HPP-CMP), although it was originally proposed to catalyze the C-methylation of 2-hydroxyethylphosphonate to give 2-hydroxypropylphosphonate in the biosynthesis of a unique C-P bond containing antibiotic fosfomycin in Streptomyces. Unexpectedly, the Fom3 reaction product from HEP-CMP was almost a 1:1 diastereomeric mixture of HPP-CMP, indicating that the C-methylation is not stereoselective. Presumably, only the CMP moiety of HEP-CMP is critical for substrate recognition; on the other hand, the enzyme does not fix the 2-hydroxy group of the substrate and either of the prochiral hydrogen atoms at the C2 position can be abstracted by the 5'-deoxyadenosyl radical generated from SAM to form the substrate radical intermediates, which react with MeCbl to afford the corresponding products. This strict substrate recognition mechanism with no stereoselectivity of a MeCbl-dependent radical SAM methyltransferase is remarkable in natural product biosynthetic chemistry, because such a hidden clue for selective substrate recognition is likely to be found in the other biosynthetic pathways. << Less

Biochemistry 56:3519-3522(2017) [PubMed] [EuropePMC]
C-Methylation Catalyzed by Fom3, a Cobalamin-Dependent Radical S-adenosyl-l-methionine Enzyme in Fosfomycin Biosynthesis, Proceeds with Inversion of Configuration.

Sato S., Kudo F., Kuzuyama T., Hammerschmidt F., Eguchi T.

Fom3, a cobalamin-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase, catalyzes C-methylation at the C2 position of cytidylylated 2-hydroxyethylphosphonate (HEP-CMP) to afford cytidylylated 2-hydroxypropylphosphonate (HPP-CMP) in fosfomycin biosynthesis. In this study, the Fom3 reac ... >> More

Fom3, a cobalamin-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase, catalyzes C-methylation at the C2 position of cytidylylated 2-hydroxyethylphosphonate (HEP-CMP) to afford cytidylylated 2-hydroxypropylphosphonate (HPP-CMP) in fosfomycin biosynthesis. In this study, the Fom3 reaction product HPP-CMP was reanalyzed by chiral ligand exchange chromatography to confirm its stereochemistry. The Fom3 methylation product was found to be ( S)-HPP-CMP only, indicating that the stereochemistry of the C-methylation catalyzed by Fom3 is ( S)-selective. In addition, Fom3 reaction was performed with ( S)-[2-2H1]HEP-CMP and ( R)-[2-2H1]HEP-CMP to elucidate the stereoselectivity during the abstraction of the hydrogen atom from C2 of HEP-CMP. Liquid chromatography-electrospray ionization mass spectrometry analysis of the 5'-deoxyadenosine produced showed that the 2H atom of ( R)-[2-2H1]HEP-CMP was incorporated into 5'-deoxyadenosine but that from ( S)-[2-2H1]HEP-CMP was not. Retention of the 2H atom of ( S)-[2-2H1]HEP-CMP in HPP-CMP was also observed. These results indicate that the 5'-deoxyadenosyl radical stereoselectively abstracts the pro-R hydrogen atom at the C2 position of HEP-CMP and the substrate radical intermediate reacts with the methyl group on cobalamin that is located on the opposite side of the substrate from SAM. Consequently, it was clarified that the C-methylation catalyzed by Fom3 proceeds with inversion of configuration. << Less

Biochemistry 57:4963-4966(2018) [PubMed] [EuropePMC]

Reaction participants Show >> << Hide

Cross-references

Publications

A (re)discovery of the Fom3 substrate.

Methylcobalamin-dependent radical SAM C-methyltransferase Fom3 recognizes cytidylyl-2-hydroxyethylphosphonate and catalyzes the nonstereoselective C-methylation in fosfomycin biosynthesis.

C-Methylation Catalyzed by Fom3, a Cobalamin-Dependent Radical S-adenosyl-l-methionine Enzyme in Fosfomycin Biosynthesis, Proceeds with Inversion of Configuration.