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- Name help_outline (S)-3-(indol-3-ylmethyl)-6,7,8,8a-tetrahydropyrrolo[1,2-a]pyrazin-1-one Identifier CHEBI:145652 Charge 0 Formula C16H17N3O InChIKeyhelp_outline FJRBFGWVEWZBJD-HNNXBMFYSA-N SMILEShelp_outline C1(=CNC2=C1C=CC=C2)CC3=CN4[C@H](C(N3)=O)CCC4 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline dimethylallyl diphosphate Identifier CHEBI:57623 (Beilstein: 5288443; CAS: 22679-02-3) help_outline Charge -3 Formula C5H9O7P2 InChIKeyhelp_outline CBIDRCWHNCKSTO-UHFFFAOYSA-K SMILEShelp_outline CC(C)=CCOP([O-])(=O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 77 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (S)-3-{[2-(1,1-dimethylallyl)-indol-3-yl]methyl}-6,7,8,8a-tetrahydropyrrolo[1,2-a]pyrazin-1-one Identifier CHEBI:145655 Charge 0 Formula C21H25N3O InChIKeyhelp_outline ILMMVPUJKFMUIW-SFHVURJKSA-N SMILEShelp_outline C1(=C(NC2=C1C=CC=C2)C(C=C)(C)C)CC3=CN4[C@H](C(N3)=O)CCC4 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 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 1,085 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:62288 | RHEA:62289 | RHEA:62290 | RHEA:62291 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Fungal indole alkaloid biogenesis through evolution of a bifunctional reductase/Diels-Alderase.
Dan Q., Newmister S.A., Klas K.R., Fraley A.E., McAfoos T.J., Somoza A.D., Sunderhaus J.D., Ye Y., Shende V.V., Yu F., Sanders J.N., Brown W.C., Zhao L., Paton R.S., Houk K.N., Smith J.L., Sherman D.H., Williams R.M.
Prenylated indole alkaloids such as the calmodulin-inhibitory malbrancheamides and anthelmintic paraherquamides possess great structural diversity and pharmaceutical utility. Here, we report complete elucidation of the malbrancheamide biosynthetic pathway accomplished through complementary approac ... >> More
Prenylated indole alkaloids such as the calmodulin-inhibitory malbrancheamides and anthelmintic paraherquamides possess great structural diversity and pharmaceutical utility. Here, we report complete elucidation of the malbrancheamide biosynthetic pathway accomplished through complementary approaches. These include a biomimetic total synthesis to access the natural alkaloid and biosynthetic intermediates in racemic form and in vitro enzymatic reconstitution to provide access to the natural antipode (+)-malbrancheamide. Reductive cleavage of an L-Pro-L-Trp dipeptide from the MalG non-ribosomal peptide synthetase (NRPS) followed by reverse prenylation and a cascade of post-NRPS reactions culminates in an intramolecular [4+2] hetero-Diels-Alder (IMDA) cyclization to furnish the bicyclo[2.2.2]diazaoctane scaffold. Enzymatic assembly of optically pure (+)-premalbrancheamide involves an unexpected zwitterionic intermediate where MalC catalyses enantioselective cycloaddition as a bifunctional NADPH-dependent reductase/Diels-Alderase. The crystal structures of substrate and product complexes together with site-directed mutagenesis and molecular dynamics simulations demonstrate how MalC and PhqE (its homologue from the paraherquamide pathway) catalyse diastereo- and enantioselective cyclization in the construction of this important class of secondary metabolites. << Less
Nat. Chem. 11:972-980(2019) [PubMed] [EuropePMC]
This publication is cited by 11 other entries.