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- Name help_outline (R)-3-phenyllactate Identifier CHEBI:11009 Charge -1 Formula C9H9O3 InChIKeyhelp_outline VOXXWSYKYCBWHO-MRVPVSSYSA-M SMILEShelp_outline O[C@H](Cc1ccccc1)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 6 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ATP Identifier CHEBI:30616 (Beilstein: 3581767) help_outline Charge -4 Formula C10H12N5O13P3 InChIKeyhelp_outline ZKHQWZAMYRWXGA-KQYNXXCUSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,280 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-leucine Identifier CHEBI:57427 Charge 0 Formula C6H13NO2 InChIKeyhelp_outline ROHFNLRQFUQHCH-YFKPBYRVSA-N SMILEShelp_outline CC(C)C[C@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 44 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 868 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline AMP Identifier CHEBI:456215 Charge -2 Formula C10H12N5O7P InChIKeyhelp_outline UDMBCSSLTHHNCD-KQYNXXCUSA-L SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 508 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline diphosphate Identifier CHEBI:33019 (Beilstein: 185088) help_outline Charge -3 Formula HO7P2 InChIKeyhelp_outline XPPKVPWEQAFLFU-UHFFFAOYSA-K SMILEShelp_outline OP([O-])(=O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,129 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 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline PF1022B Identifier CHEBI:180462 Charge 0 Formula C64H84N4O12 InChIKeyhelp_outline ILQZHPWFOWCYND-SQZSLCRCSA-N SMILEShelp_outline C1(O[C@@H](C(N([C@H](C(O[C@@H](C(N([C@H](C(O[C@@H](C(N([C@H](C(O[C@@H](C(N([C@H]1CC(C)C)C)=O)CC=2C=CC=CC2)=O)CC(C)C)C)=O)CC=3C=CC=CC3)=O)CC(C)C)C)=O)CC=4C=CC=CC4)=O)CC(C)C)C)=O)CC=5C=CC=CC5)=O 2D coordinates Mol file for the small molecule Search links Involved in 1 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 792 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:68756 | RHEA:68757 | RHEA:68758 | RHEA:68759 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Biosynthesis of PF1022A and related cyclooctadepsipeptides.
Weckwerth W., Miyamoto K., Iinuma K., Krause M., Glinski M., Storm T., Bonse G., Kleinkauf H., Zocher R.
PF1022A belongs to a recently identified class of N-methylated cyclooctadepsipeptides (CODPs) with strong anthelmintic properties. Described here is the cell-free synthesis of this CODP and related structures, as well as the purification and enzymatic characterization of the responsible synthetase ... >> More
PF1022A belongs to a recently identified class of N-methylated cyclooctadepsipeptides (CODPs) with strong anthelmintic properties. Described here is the cell-free synthesis of this CODP and related structures, as well as the purification and enzymatic characterization of the responsible synthetase. For PF1022A synthesis extracts of Mycelia sterilia were incubated with the precursors L-leucine, D-lactate, D-phenyllactate, and S-adenosyl-L-methionine in the presence of ATP and MgCl(2). A 350-kDa depsipeptide synthetase, PFSYN, responsible for PF1022A synthesis was purified to electrophoretic homogeneity. Like other peptide synthetases, PFSYN follows a thiotemplate mechanism in which the substrates are activated as thioesters via adenylation. N-Methylation of the substrate L-leucine takes place after covalent binding prior to peptide bond formation. The enzyme is capable of synthesizing all known natural cyclooctadepsipeptides of the PF1022 type (A, B, C, and D) differing in the content of D-lactate and D-phenyllactate. In addition to PF1022 types A, B, C, and D, the in vitro incubations produced PF1022F (a CODP consisting of D-lactate and N-methyl-L-leucine), as well as di-, tetra-, and hexa-PF1022 homologs. PFSYN strongly resembles the well documented enniatin synthetase in size and mechanism. Our results suggest that PFSYN, like enniatin synthetase, is an enzyme with two peptide synthetase domains and forms CODP by repeated condensation of dipeptidol building blocks. Due to the low specificity of the d-hydroxy acid binding site, D-lactate or D-phenyllactate can be incorporated into the dipeptidols depending on the concentration of these substrates in the reaction mixture. << Less
J. Biol. Chem. 275:17909-17915(2000) [PubMed] [EuropePMC]
This publication is cited by 4 other entries.
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In vitro synthesis of new cyclodepsipeptides of the PF1022-type: probing the alpha-D-hydroxy acid tolerance of PF1022 synthetase.
Mueller J., Feifel S.C., Schmiederer T., Zocher R., Suessmuth R.D.
The nonribosomal peptide synthetase PF1022-synthetase (PFSYN) synthesises the cyclooctadepsipeptide PF1022 from the building blocks D-lactate, D-phenyllactate and N-methylleucine. The substrate tolerance of PFSYN for hydroxy acids was probed by in vitro screening of a set of aliphatic and aromatic ... >> More
The nonribosomal peptide synthetase PF1022-synthetase (PFSYN) synthesises the cyclooctadepsipeptide PF1022 from the building blocks D-lactate, D-phenyllactate and N-methylleucine. The substrate tolerance of PFSYN for hydroxy acids was probed by in vitro screening of a set of aliphatic and aromatic alpha-D-hydroxy acids with various structural modifications in the side chain. Thus, new PF1022 derivatives for example, propargyl-D-lactyl-PF1022 and beta-thienyl-D-lactyl-PF1022 were generated. The promiscuous behaviour of PFSYN towards aliphatic and aromatic alpha-D-hydroxy acids is considerably larger than that of related enniatin synthetase (ESYN) and thus gives rise to the enzymatic generation of various new PF1022 derivatives. << Less
ChemBioChem 10:323-328(2009) [PubMed] [EuropePMC]
This publication is cited by 4 other entries.
Comments
This reaction starts by the activation of the substrate by ATP to form substrate-adenylate. The second step is the ligation of the substrate to the carrier domain of the NRPS (nonribosomal peptide synthetase) enzyme followed by elongation and cyclisation to form the product.