Rhea - reaction knowledgebase

Enzymes

UniProtKB

Reaction participants Show >> << Hide

Name ^help_outline acetyl-CoA Identifier CHEBI:57288 (Beilstein: 8468140) ^help_outline Charge -4 Formula C23H34N7O17P3S InChIKey^help_outline ZSLZBFCDCINBPY-ZSJPKINUSA-J SMILES^help_outline CC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 321 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 InChIKey^help_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILES^help_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 holo-[ACP] Identifier RHEA-COMP:9685 Reactive part ^help_outline
- Name ^help_outline O-(pantetheine-4ʼ-phosphoryl)-L-serine residue Identifier CHEBI:64479 Charge -1 Formula C14H25N3O8PS SMILES^help_outline C(NC(CCNC(=O)[C@@H](C(COP(OC[C@@H](C(*)=O)N*)(=O)[O-])(C)C)O)=O)CS 2D coordinates Mol file for the small molecule Search links Involved in 189 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 116 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline malonyl-CoA Identifier CHEBI:57384 Charge -5 Formula C24H33N7O19P3S InChIKey^help_outline LTYOQGRJFJAKNA-DVVLENMVSA-I SMILES^help_outline CC(C)(COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 211 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name^help_outline 3-(2,4-dioxopentyl)-3,6,8,9-tetrahydroxy-1-oxo-1,2,3,4-tetrahydroanthracene-2-carboxyl-[ACP] Identifier RHEA-COMP:16518 Reactive part ^help_outline
- Name ^help_outline O-(S-3-(2,4-dioxopentyl)-3,6,8,9-tetrahydroxy-1-oxo-1,2,3,4-tetrahydroanthracene-2-carboxylpantetheine-4ʼ-phosphoryl)-L-serine residue Identifier CHEBI:149687 Charge -1 Formula C34H41N3O16PS SMILES^help_outline C=1(C2=C(C=C(C1)O)C=C3C(=C2O)C(C(C(C3)(CC(CC(C)=O)=O)O)C(=O)SCCNC(CCNC(=O)[C@@H](C(COP(OC[C@@H](C(*)=O)N*)(=O)[O-])(C)C)O)=O)=O)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
Search links Involved in 2 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline CO₂ Identifier CHEBI:16526 (Beilstein: 1900390; CAS: 124-38-9) ^help_outline Charge 0 Formula CO2 InChIKey^help_outline CURLTUGMZLYLDI-UHFFFAOYSA-N SMILES^help_outline O=C=O 2D coordinates Mol file for the small molecule Search links Involved in 980 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline CoA Identifier CHEBI:57287 (Beilstein: 11604429) ^help_outline Charge -4 Formula C21H32N7O16P3S InChIKey^help_outline RGJOEKWQDUBAIZ-IBOSZNHHSA-J SMILES^help_outline CC(C)(COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@@H](O)C(=O)NCCC(=O)NCCS 2D coordinates Mol file for the small molecule Search links Involved in 1,468 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline H₂O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) ^help_outline Charge 0 Formula H2O InChIKey^help_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILES^help_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:64088	RHEA:64089	RHEA:64090	RHEA:64091
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	2 proteins	2 proteins

Publications

Comparative characterization of fungal anthracenone and naphthacenedione biosynthetic pathways reveals an alpha-hydroxylation-dependent Claisen-like cyclization catalyzed by a dimanganese thioesterase.

Li Y., Chooi Y.H., Sheng Y., Valentine J.S., Tang Y.

The linear tetracyclic TAN-1612 (1) and BMS-192548 (2) were isolated from different filamentous fungal strains and have been examined as potential neuropeptide Y and neurokinin-1 receptor antagonists, respectively. Although the biosynthesis of fungal aromatic polyketides has attracted much interes ... >> More

The linear tetracyclic TAN-1612 (1) and BMS-192548 (2) were isolated from different filamentous fungal strains and have been examined as potential neuropeptide Y and neurokinin-1 receptor antagonists, respectively. Although the biosynthesis of fungal aromatic polyketides has attracted much interest in recent years, the biosynthetic mechanism for such naphthacenedione-containing products has not been established. Using a targeted genome mining approach, we first located the ada gene cluster responsible for the biosynthesis of 1 in Aspergillus niger ATCC 1015. The connection between 1 and the ada pathway was verified through overexpression of the Zn(2)Cys(6)-type pathway-specific transcriptional regulator AdaR and subsequent gene expression analysis. The enzymes encoded in the ada gene cluster share high sequence similarities to the known apt pathway linked to the biosynthesis of anthraquinone asperthecin 3. Subsequent comparative investigation of these two highly homologous gene clusters by heterologous pathway reconstitution in Saccharomyces cerevisiae revealed a novel α-hydroxylation-dependent Claisen cyclization cascade, which involves a flavin-dependent monooxygenase that hydroxylates the α-carbon of an acyl carrier protein-bound polyketide and a bifunctional metallo-β-lactamase-type thioesterase (MβL-TE). The bifunctional MβL-TE catalyzes the fourth ring cyclization to afford the naphthacenedione scaffold upon α-hydroxylation, whereas it performs hydrolytic release of an anthracenone product in the absence of α-hydroxylation. Through in vitro biochemical characterizations and metal analyses, we verified that the apt MβL-TE is a dimanganese enzyme and requires both Mn(2+) cations for the observed activities. The MβL-TE is the first example of a thioesterase in polyketide biosynthesis that catalyzes the Claisen-like condensation without an α/β hydrolase fold and forms no covalent bond with the substrate. These mechanistic features should be general to the biosynthesis of tetracyclic naphthacenedione compounds in fungi. << Less

J. Am. Chem. Soc. 133:15773-15785(2011) [PubMed] [EuropePMC]

This publication is cited by 7 other entries.

RHEA:64088 acetyl-CoA + 9 H(+) + holo-[ACP] + 9 malonyl-CoA = 3-(2,4-dioxopentyl)-3,6,8,9-tetrahydroxy-1-oxo-1,2,3,4-tetrahydroanthracene-2-carboxyl-[ACP] + 9 CO2 + 10 CoA + 2 H2O

Enzymes

Reaction participants Show >> << Hide

Cross-references

Publications

Comparative characterization of fungal anthracenone and naphthacenedione biosynthetic pathways reveals an alpha-hydroxylation-dependent Claisen-like cyclization catalyzed by a dimanganese thioesterase.