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- Name help_outline 1-hydroxy-3-{[2-(1,1-dimethylallyl)-indol-3-yl]methyl}-4H,6H,7H,8H-pyrrolo[1,2-a]pyrazine Identifier CHEBI:145675 Charge 1 Formula C21H26N3O InChIKeyhelp_outline IBZVLSUKARHHFO-UHFFFAOYSA-O SMILEShelp_outline C1(=C(NC2=C1C=CC=C2)C(C=C)(C)C)CC=3CN4C(=C([NH+]3)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 (+)-premalbrancheamide Identifier CHEBI:145658 Charge 1 Formula C21H26N3O InChIKeyhelp_outline LBTZXCFDJFHPMI-DQLDELGASA-O SMILEShelp_outline C1=C2C(=CC=C1)C3=C(N2)C([C@]4([C@@]5(C3)C[NH+]6[C@](C4)(CCC6)C(N5)=O)[H])(C)C 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
Cross-references
| RHEA:62304 | RHEA:62305 | RHEA:62306 | RHEA:62307 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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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.