Enzymes
| UniProtKB help_outline | 2 proteins |
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- Name help_outline dodecanoyl-CoA Identifier CHEBI:57375 Charge -4 Formula C33H54N7O17P3S InChIKeyhelp_outline YMCXGHLSVALICC-GMHMEAMDSA-J SMILEShelp_outline CCCCCCCCCCCC(=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 40 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 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline malonyl-CoA Identifier CHEBI:57384 Charge -5 Formula C24H33N7O19P3S InChIKeyhelp_outline LTYOQGRJFJAKNA-DVVLENMVSA-I SMILEShelp_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 4-hydroxy-6-(2-oxotridecyl)pyran-2-one Identifier CHEBI:84150 Charge 0 Formula C18H28O4 InChIKeyhelp_outline GPSLPPYNZMBYDU-UHFFFAOYSA-N SMILEShelp_outline CCCCCCCCCCCC(=O)Cc1cc(O)cc(=O)o1 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 CO2 Identifier CHEBI:16526 (Beilstein: 1900390; CAS: 124-38-9) help_outline Charge 0 Formula CO2 InChIKeyhelp_outline CURLTUGMZLYLDI-UHFFFAOYSA-N SMILEShelp_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 InChIKeyhelp_outline RGJOEKWQDUBAIZ-IBOSZNHHSA-J SMILEShelp_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
Cross-references
| RHEA:43368 | RHEA:43369 | RHEA:43370 | RHEA:43371 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Promiscuous fatty acyl CoA ligases produce acyl-CoA and acyl-SNAC precursors for polyketide biosynthesis.
Arora P., Vats A., Saxena P., Mohanty D., Gokhale R.S.
The study of bioactive natural products has undergone rapid advancement with the cloning and sequencing of large number of gene clusters and the concurrent progress to manipulate complex biosynthetic systems in heterologous hosts. The genetic reconstitution necessitates that the heterologous hosts ... >> More
The study of bioactive natural products has undergone rapid advancement with the cloning and sequencing of large number of gene clusters and the concurrent progress to manipulate complex biosynthetic systems in heterologous hosts. The genetic reconstitution necessitates that the heterologous hosts possess substrate pools that could be coordinately supplied for biosynthesis. Polyketide synthases (PKS) utilize acyl-coenzyme A (CoA) precursors and synthesize polyketides by repetitive decarboxylative condensations. Here we show that acyl-CoA ligases, which belong to a large family of acyl-activating enzymes, possess potential to produce varied starter CoA precursors that could be utilized in polyketide biosynthesis. Incidentally, such protein domains have been recognized in several PKS and nonribosomal peptide synthetase gene clusters. Our studies with mycobacterial fatty acyl-CoA ligases (FACLs) show remarkable tolerance to activate a variety of fatty acids that contain modifications at alpha, beta, omega, and omega-nu positions. This substrate flexibility extends further such that these proteins also efficiently utilize N-acetyl cysteamine, the shorter acceptor terminal portion of CoASH, to produce acyl-SNACs. We show that the in situ generated acyl-CoAs and acyl-SNACs could be channeled to types I and -III PKS systems to produce new metabolites. Together, the promiscuous activity of FACL and PKSs provides new opportunities to expand the repertoire of natural products. << Less
J. Am. Chem. Soc. 127:9388-9389(2005) [PubMed] [EuropePMC]
This publication is cited by 33 other entries.
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A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.
Sankaranarayanan R., Saxena P., Marathe U.B., Gokhale R.S., Shanmugam V.M., Rukmini R.
The superfamily of plant and bacterial type III polyketide synthases (PKSs) produces diverse metabolites with distinct biological functions. PKS18, a type III PKS from Mycobacterium tuberculosis, displays an unusual broad specificity for aliphatic long-chain acyl-coenzyme A (acyl-CoA) starter unit ... >> More
The superfamily of plant and bacterial type III polyketide synthases (PKSs) produces diverse metabolites with distinct biological functions. PKS18, a type III PKS from Mycobacterium tuberculosis, displays an unusual broad specificity for aliphatic long-chain acyl-coenzyme A (acyl-CoA) starter units (C(6)-C(20)) to produce tri- and tetraketide pyrones. The crystal structure of PKS18 reveals a 20 A substrate binding tunnel, hitherto unidentified in this superfamily of enzymes. This remarkable tunnel extends from the active site to the surface of the protein and is primarily generated by subtle changes of backbone dihedral angles in the core of the protein. Mutagenic studies combined with structure determination provide molecular insights into the structural elements that contribute to the chain length specificity of the enzyme. This first bacterial type III PKS structure underlines a fascinating example of the way in which subtle changes in protein architecture can generate metabolite diversity in nature. << Less
Nat. Struct. Mol. Biol. 11:894-900(2004) [PubMed] [EuropePMC]
This publication is cited by 5 other entries.
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A new family of type III polyketide synthases in Mycobacterium tuberculosis.
Saxena P., Yadav G., Mohanty D., Gokhale R.S.
The Mycobacterium tuberculosis genome has revealed a remarkable array of polyketide synthases (PKSs); however, no polyketide product has been isolated thus far. Most of the PKS genes have been implicated in the biosynthesis of complex lipids. We report here the characterization of two novel type I ... >> More
The Mycobacterium tuberculosis genome has revealed a remarkable array of polyketide synthases (PKSs); however, no polyketide product has been isolated thus far. Most of the PKS genes have been implicated in the biosynthesis of complex lipids. We report here the characterization of two novel type III PKSs from M. tuberculosis that are involved in the biosynthesis of long-chain alpha-pyrones. Measurement of steady-state kinetic parameters demonstrated that the catalytic efficiency of PKS18 protein was severalfold higher for long-chain acyl-coenzyme A substrates as compared with the small-chain precursors. The specificity of PKS18 and PKS11 proteins toward long-chain aliphatic acyl-coenzyme A (C12 to C20) substrates is unprecedented in the chalcone synthase (CHS) family of condensing enzymes. Based on comparative modeling studies, we propose that these proteins might have evolved by fusing the catalytic machinery of CHS and beta-ketoacyl synthases, the two evolutionarily related members with conserved thiolase fold. The mechanistic and structural importance of several active site residues, as predicted by our structural model, was investigated by performing site-directed mutagenesis. The functional identification of diverse catalytic activity in mycobacterial type III PKSs provide a fascinating example of metabolite divergence in CHS-like proteins. << Less
J. Biol. Chem. 278:44780-44790(2003) [PubMed] [EuropePMC]
This publication is cited by 8 other entries.