Family Search for PF11578 (DUF3237)

PF11578 hits 17 sequences in PaperBLAST's database above the trusted cutoff. Showing hits to curated sequences only. Or see all hits or try another family.

ORF7_PENRF / W6Q4S2 PR-toxin biosynthesis cluster protein 7 from Penicillium roqueforti (strain FM164) (see 6 papers)
Aligns to 12:182 / 186 (91.9%), covers 94.0% of PF11578, 82.6 bits

• function: Part of the gene cluster that mediates the biosynthesis of PR-toxin, a bicyclic sesquiterpene belonging to the eremophilane class and acting as a mycotoxin (PubMed:24239699, PubMed:27921136). The first step of the pathway is catalyzed by the aristolochene synthase which performs the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene (PubMed:15186158, PubMed:24239699, PubMed:8440737). Following the formation of aristolochene, the non-oxygenated aristolochene is converted to the trioxygenated intermediate eremofortin B, via 7-epi-neopetasone (PubMed:24239699, PubMed:26274339). This conversion appears to involve three enzymes, a hydroxysterol oxidase-like enzyme, the quinone-oxidase prx3 that forms the quinone-type-structure in the bicyclic nucleus of aristolochene with the C8-oxo group and the C-3 hydroxyl group, and the P450 monooxygenase ORF6 that introduces the epoxide at the double bond between carbons 1 and 2 (PubMed:24239699, PubMed:27921136). No monoxy or dioxy-intermediates have been reported to be released to the broth, so these three early oxidative reactions may be coupled together (PubMed:24239699). Eremofortin B is further oxidized by another P450 monooxygenase, that introduces a second epoxide between carbons 7 and 11 prior to acetylation to eremofortin A by the acetyltransferase ORF8 (PubMed:16345540, PubMed:24239699, PubMed:27921136). The second epoxidation may be performed by a second P450 monooxygenase (PubMed:24239699). After the acetylation step, eremofortin A is converted to eremofortin C and then to PR-toxin (PubMed:24239699). First the conversion of eremofortin A to eremofortin C proceeds by oxidation of the side chain of the molecule at C-12 and is catalyzed by the short-chain oxidoreductase prx1 (PubMed:16345540, PubMed:24239699). The cytochrome P450 monooxygenase ORF6 is probably also involved in this step (PubMed:27921136). The primary alcohol formed at C-12 is finally oxidized by the short-chain alcohol dehydrogenase prx4 that forms PR-toxin (PubMed:16345540, PubMed:24239699).

PHNH_PENHR / A0A1S6PUA4 Hydroalkoxylation enzyme phnH; Phenalenone biosynthesis cluster protein H; EC 4.-.-.- from Penicillium herquei (see 2 papers)
Aligns to 24:145 / 149 (81.9%), covers 56.4% of PF11578, 55.3 bits

• function: Hydroalkoxylation enzyme; part of the gene cluster that mediates the biosynthesis of phenalenones such as herqueinone, compounds that have been reported to treat tumors, bacterial infections and/or mycoses, and rheumatic diseases (PubMed:26978228). The non- reducing polyketide synthase phnA synthesizes the heptaketide backbone and cyclizes it into the angular, hemiketal-containing naphtho-gamma- pyrone prephenalenone. The product template (PT) domain of phnA catalyzes only the C4-C9 aldol condensation, which is unprecedented among known PT domains (PubMed:26978228, PubMed:28240554). The transformation of prephenalenone to phenalenones requires an FAD- dependent monooxygenase phnB, which catalyzes the C2 aromatic hydroxylation of prephenalenone and ring opening of the gamma-pyrone ring simultaneously (PubMed:26978228, PubMed:28240554). Subsequent intramolecular deprotonation of C3 phenolic oxygen accelerates phenalenone ring closure to yield the tricyclic phenalenone core with a C2 hydroxylation (PubMed:26978228, PubMed:28240554). The prenyltransferase phnF further catalyzes reverse C-prenylation of phenalenone by direct electrophilic substitution at C6, or possibly via first a forward O-prenylation of a neighboring phenol in phenalenone, followed by a Claisen rearrangement (PubMed:28240554). The hydroalkoxylation enzyme phnH catalyzes the 5-exo-trigcyclization via acid catalysis after the spontaneous deprotonation of 7-OH, which leads to the formation of the dihydrobenzofuran atrovenetin (PubMed:28240554). Atrovenetin is further converted to deoxyherqueinone by the O-methyltransferase phnC which can methylate C2-OH to stabilize the northern portion of the phenalenone core (PubMed:28240554). Finally, the oxidoreductase phnG converts deoxyherqueinone to herqueinone via C6 hydroxylation (PubMed:28240554).
  catalytic activity: 2,4,7,9-tetrahydroxy-6-methyl-8-(2-methylbut-3-en-2-yl)-1-oxo- 1H-phenalen-3-ol = (2'R)-atrovenetin (RHEA:62660)

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