Pyoluteorin

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Pyoluteorin
Molecule of pyoluteorin
Identifiers
  • (4,5-Dichloro-1H-pyrrol-2-yl)-(2,6-dihydroxyphenyl)methanone
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 checkY
  • Key:JPGWTZORMBTNMF-UHFFFAOYSA-N checkY

Pyoluteorin is a natural

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.

References