Pyoluteorin

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Pyoluteorin
Pyoluteorin.svg
Identifiers
  • (4,5-Dichloro-1H-pyrrol-2-yl)-(2,6-dihydroxyphenyl)methanone
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)
  • C1=CC(=C(C(=C1)O)C(=O)C2=CC(=C(N2)Cl)Cl)O
  • InChI=InChI=1S/C11H7Cl2NO3/c12-5-4-6(14-11(5)13)10(17)9-7(15)2-1-3-8(9)16/h1-4,14-16H Yes check.svgY
  • Key:JPGWTZORMBTNMF-UHFFFAOYSA-N Yes check.svgY

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]

Biosynthesis

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.

Pyoluteorin biosynthesis. Asterisk denotes inactive domain. Pyoluteorin Biosynthesis copy.png
Pyoluteorin biosynthesis. Asterisk denotes inactive domain.

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References

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