Enzymes
| UniProtKB help_outline | 1 proteins |
| Enzyme class help_outline |
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Reaction participants Show >> << Hide
- Name help_outline AH2 Identifier CHEBI:17499 Charge 0 Formula RH2 SMILEShelp_outline *([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 2,713 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 InChIKeyhelp_outline ODFOOQGQRDVSPW-PEBGCTIMSA-L SMILEShelp_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 InChIKeyhelp_outline MEFKEPWMEQBLKI-AIRLBKTGSA-O SMILEShelp_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 842 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 InChIKeyhelp_outline XGYIMTFOTBMPFP-KQYNXXCUSA-N SMILEShelp_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 66 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 SMILEShelp_outline * 2D coordinates Mol file for the small molecule Search links Involved in 2,783 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 InChIKeyhelp_outline VQDRQBLAARRQFV-CNYIRLTGSA-L SMILEShelp_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 InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 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 InChIKeyhelp_outline FFEARJCKVFRZRR-BYPYZUCNSA-N SMILEShelp_outline CSCC[C@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 118 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 InChIKeyhelp_outline ZJUKTBDSGOFHSH-WFMPWKQPSA-N SMILEShelp_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 768 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 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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A (re)discovery of the Fom3 substrate.
Blaszczyk A.J., Booker S.J.
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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
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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-<sup>2</sup>H<sub>1</sub>]HEP-CMP and ( R)-[2-<sup>2</sup>H<sub>1</sub>]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 <sup>2</sup>H atom of ( R)-[2-<sup>2</sup>H<sub>1</sub>]HEP-CMP was incorporated into 5'-deoxyadenosine but that from ( S)-[2-<sup>2</sup>H<sub>1</sub>]HEP-CMP was not. Retention of the <sup>2</sup>H atom of ( S)-[2-<sup>2</sup>H<sub>1</sub>]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