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.
^Gross H, Loper JE (November 2009). "Genomics of secondary metabolite production by Pseudomonas spp". Natural Product Reports. 26 (11): 1408–46.
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^Takeda R (1958). "Structure of a new antibiotic, pyoluteorin". Journal of the American Chemical Society. 80 (17): 4749–4750.
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^Maurhofer M (September 10, 1991). "Influence of Enhanced Antibiotic Production in Pseudomonas fluorescens Strain CHA0 on its Disease Suppressive Capacity". Phytopathology. 82 (2): 190–195.
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10.1094/Phyto-82-190.
^Howell CR (January 16, 1980). "Suppression of Pythium ultimum-induced damping-off of cotton seedlings by pseudomonas fluorescens and its antibiotic, pyoluteorin". Phytopathology. 70 (8): 712–715.
doi:
10.1094/Phyto-70-712.
^Doi K (October 2014). "Characterization of pyoluteorin derivatives as Mcl-1 antagonists". Cancer Research. 74 (19): 1805.
doi:
10.1158/1538-7445.AM2014-1805.
^Nowak-Thompson B, Gould SJ, Loper JE (December 1997). "Identification and sequence analysis of the genes encoding a polyketide synthase required for pyoluteorin biosynthesis in Pseudomonas fluorescens Pf-5". Gene. 204 (1–2): 17–24.
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