InChI=1S/C12H21N3O11P2/c1- 6(16)5-27(20,21)26-28(22,23)24-4-7-9(17)10(18)11(25-7)15-3-2-8(13)14-12(15)19/h2-3,6-7,9-11,16-18H,4-5H2,1H3,(H,20,21)(H,22,23)(H2,13,14,19)/p-2/t6-,7+,9+,10+,11+/m0/s1 |
| VQDRQBLAARRQFV-CNYIRLTGSA-L |
| 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 |
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Outgoing
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cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate)(2−)
(CHEBI:142877)
has functional parent
cytidine 5'-monophosphate(2−)
(CHEBI:60377)
cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate)(2−)
(CHEBI:142877)
is a
organic molecular entity
(CHEBI:50860)
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cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate)
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UniProt
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CPD-21482
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MetaCyc accession
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| View more database links |
Blaszczyk AJ, Booker SJ (2018)
A (Re)Discovery of the Fom3 Substrate.
Biochemistry 57, 891-892 (Source: SUBMITTER) [PubMed:29345912] | Sato S, Kudo F, Kuzuyama T, Hammerschmidt F, Eguchi T (2018)
C-Methylation Catalyzed by Fom3, a Cobalamin-Dependent Radical S-adenosyl-l-methionine Enzyme in Fosfomycin Biosynthesis, Proceeds with Inversion of Configuration.
Biochemistry 57, 4963-4966 (Source: SUBMITTER) [PubMed:29966085]
[show Abstract]
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. | Sato S, Kudo F, Kim SY, Kuzuyama T, Eguchi T (2017)
Methylcobalamin-Dependent Radical SAM C-Methyltransferase Fom3 Recognizes Cytidylyl-2-hydroxyethylphosphonate and Catalyzes the Nonstereoselective C-Methylation in Fosfomycin Biosynthesis.
Biochemistry 56, 3519-3522 (Source: SUBMITTER) [PubMed:28678474]
[show Abstract]
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. |
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