5w7m

Structural highlights

Function

[ROQN_PENRW] Glandicoline B O-methyltransferase; part of the gene cluster that mediates the biosynthesis of the mycotoxin meleagrin (PubMed:22118684, PubMed:23776469). The first stage is catalyzed by the dipeptide synthase roqA which condenses histidine and tryptophan to produce histidyltryptophanyldiketopiperazine (HTD) (PubMed:22118684, PubMed:23776469). HTD is then converted to roquefortine C through two possible pathways (PubMed:23776469). In the first pathway, prenyltransferase roqD transforms HTD to the intermediate roquefortine D, which is in turn converted to roquefortine C by the cytochrome P450 monooxygenase roqR (PubMed:23776469). In the second pathway, HTD is first converted to the intermediate dehydrohistidyltryptophanyldi-ketopiperazine (DHTD) by roqR which is then prenylated by roqD to form roquefortine C (PubMed:23776469). Roquefortine C can be further transformed to meleagrin via three more reactions including oxydation to glandicolin A by roqM, which is further reduced to glandicoline B by roqO (PubMed:23776469). Finally, glandicoline B is converted to meleagrin by the glandicoline B O-methyltransferase roqN (PubMed:22118684, PubMed:23776469). More studies identified further branching and additional metabolites produced by the roquefortine/meleagrin cluster, including roquefortine F, roquefortine L, roquefortine M, roquefortine N and neoxaline (PubMed:24225953).^{[1] [2] [3]}

References

1. ↑ Garcia-Estrada C, Ullan RV, Albillos SM, Fernandez-Bodega MA, Durek P, von Dohren H, Martin JF. A single cluster of coregulated genes encodes the biosynthesis of the mycotoxins roquefortine C and meleagrin in Penicillium chrysogenum. Chem Biol. 2011 Nov 23;18(11):1499-512. doi: 10.1016/j.chembiol.2011.08.012. PMID:22118684 doi:http://dx.doi.org/10.1016/j.chembiol.2011.08.012
2. ↑ Ali H, Ries MI, Nijland JG, Lankhorst PP, Hankemeier T, Bovenberg RA, Vreeken RJ, Driessen AJ. A branched biosynthetic pathway is involved in production of roquefortine and related compounds in Penicillium chrysogenum. PLoS One. 2013 Jun 12;8(6):e65328. doi: 10.1371/journal.pone.0065328. Print 2013. PMID:23776469 doi:http://dx.doi.org/10.1371/journal.pone.0065328
3. ↑ Ries MI, Ali H, Lankhorst PP, Hankemeier T, Bovenberg RA, Driessen AJ, Vreeken RJ. Novel key metabolites reveal further branching of the roquefortine/meleagrin biosynthetic pathway. J Biol Chem. 2013 Dec 27;288(52):37289-95. doi: 10.1074/jbc.M113.512665. Epub, 2013 Nov 13. PMID:24225953 doi:http://dx.doi.org/10.1074/jbc.M113.512665