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Chemical and physical data | |
Formula | C11H7Cl2NO3 |
Molar mass | 272.08 g·mol−1 |
3D model ( JSmol) | |
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Pyoluteorin is a natural antibiotic that is biosynthesized from a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathway. [1] Pyoluteorin was first isolated in the 1950s from Pseudomonas aeruginosa strains T359 and IFO 3455 [2] and was found to be toxic against oomycetes, bacteria, fungi, and against certain plants. [3] Pyoluteorin is most notable for its toxicity against the oomycete Pythium ultimum, [4] which is a plant pathogen that causes a global loss in agriculture. Currently, pyoluteorin derivatives are being studied as an Mcl-1 antagonist in order to target cancers that have elevated Mcl-1 levels. [5]
Pyoluteorin is synthesized from an NRPS/PKS hybrid pathway. The resorcinol ring is derived from a type I PKS [6] [7] while the dichloropyrrole[ clarification needed] moiety is derived from a type II NRPS. [8] Pyoluteorin biosynthesis begins with the activation of L- proline to prolyl-AMP by the adenylation domain PltF. With prolyl-AMP still in the active site, the active form of the peptidyl carrier protein PltL binds to PltF. Then PltF catalyzes the aminoacylation of PltL by attaching L-proline to the thiol of the 4’phosphopantetheine arm of PltL. [9] Next, the dehydrogenase PltE desaturates the prolyl moiety on PltL to create pyrrolyl-PltL. The halogenation domain PltA then dichlorinates the pyrrole moiety first at position 5 and then at position 4 in a FADH2 dependent manner. [10] The dichloropyrroyl residue is then transferred to the type I PKS PltB and PltC, however, the mechanism of transfer is unknown. The addition of 3 malonyl-CoA monomers, cyclization, and release by the thioesterase PltG gives pyoluteorin.
Identifiers | |
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| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
Chemical and physical data | |
Formula | C11H7Cl2NO3 |
Molar mass | 272.08 g·mol−1 |
3D model ( JSmol) | |
| |
|
Pyoluteorin is a natural antibiotic that is biosynthesized from a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathway. [1] Pyoluteorin was first isolated in the 1950s from Pseudomonas aeruginosa strains T359 and IFO 3455 [2] and was found to be toxic against oomycetes, bacteria, fungi, and against certain plants. [3] Pyoluteorin is most notable for its toxicity against the oomycete Pythium ultimum, [4] which is a plant pathogen that causes a global loss in agriculture. Currently, pyoluteorin derivatives are being studied as an Mcl-1 antagonist in order to target cancers that have elevated Mcl-1 levels. [5]
Pyoluteorin is synthesized from an NRPS/PKS hybrid pathway. The resorcinol ring is derived from a type I PKS [6] [7] while the dichloropyrrole[ clarification needed] moiety is derived from a type II NRPS. [8] Pyoluteorin biosynthesis begins with the activation of L- proline to prolyl-AMP by the adenylation domain PltF. With prolyl-AMP still in the active site, the active form of the peptidyl carrier protein PltL binds to PltF. Then PltF catalyzes the aminoacylation of PltL by attaching L-proline to the thiol of the 4’phosphopantetheine arm of PltL. [9] Next, the dehydrogenase PltE desaturates the prolyl moiety on PltL to create pyrrolyl-PltL. The halogenation domain PltA then dichlorinates the pyrrole moiety first at position 5 and then at position 4 in a FADH2 dependent manner. [10] The dichloropyrroyl residue is then transferred to the type I PKS PltB and PltC, however, the mechanism of transfer is unknown. The addition of 3 malonyl-CoA monomers, cyclization, and release by the thioesterase PltG gives pyoluteorin.