7wh9

Structural highlights

Function

GEDA_ASPTN O-methyltransferase; part of the gene cluster that mediates the biosynthesis of geodin, an intermediate in the biosynthesis of other natural products (PubMed:7665560, PubMed:19549600, PubMed:24009710). The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase (PKS) gedC (PubMed:12536215, PubMed:19549600). The atrochrysone carboxyl ACP thioesterase gedB then breaks the thioester bond and releases the atrochrysone carboxylic acid from gedC (PubMed:19549600). The atrochrysone carboxylic acid is then converted to atrochrysone which is further transformed into emodinanthrone (PubMed:24009710). The next step is performed by the emodinanthrone oxygenase gedH that catalyzes the oxidation of emodinanthrone to emodin (PubMed:1810248). Emodin O-methyltransferase encoded probably by gedA then catalyzes methylation of the 8-hydroxy group of emodin to form questin (PubMed:1444712). Ring cleavage of questin by questin oxidase gedK leads to desmethylsulochrin via several intermediates including questin epoxide (PubMed:3182756). Another methylation step probably catalyzed by methyltransferase gedG leads to the formation of sulochrin which is further converted to dihydrogeodin by the sulochrin halogenase gedL (PubMed:24009710). Finally, the dihydrogeodin oxidase gedJ catalyzes the stereospecific phenol oxidative coupling reaction converting dihydrogeodin to geodin (PubMed:7665560).^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Askenazi M, Driggers EM, Holtzman DA, Norman TC, Iverson S, Zimmer DP, Boers ME, Blomquist PR, Martinez EJ, Monreal AW, Feibelman TP, Mayorga ME, Maxon ME, Sykes K, Tobin JV, Cordero E, Salama SR, Trueheart J, Royer JC, Madden KT. Integrating transcriptional and metabolite profiles to direct the engineering of lovastatin-producing fungal strains. Nat Biotechnol. 2003 Feb;21(2):150-6. doi: 10.1038/nbt781. Epub 2003 Jan 21. PMID:12536215 doi:http://dx.doi.org/10.1038/nbt781
2. ↑ Chen ZG, Fujii I, Ebizuka Y, Sankawa U. Emodin O-methyltransferase from Aspergillus terreus. Arch Microbiol. 1992;158(1):29-34. doi: 10.1007/BF00249062. PMID:1444712 doi:http://dx.doi.org/10.1007/BF00249062
3. ↑ Fujii I, Chen ZG, Ebizuka Y, Sankawa U. Identification of emodinanthrone oxygenase in fungus Aspergillus terreus. Biochem Int. 1991 Dec;25(6):1043-9. PMID:1810248
4. ↑ Awakawa T, Yokota K, Funa N, Doi F, Mori N, Watanabe H, Horinouchi S. Physically discrete beta-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase. Chem Biol. 2009 Jun 26;16(6):613-23. doi: 10.1016/j.chembiol.2009.04.004. PMID:19549600 doi:http://dx.doi.org/10.1016/j.chembiol.2009.04.004
5. ↑ Nielsen MT, Nielsen JB, Anyaogu DC, Holm DK, Nielsen KF, Larsen TO, Mortensen UH. Heterologous reconstitution of the intact geodin gene cluster in Aspergillus nidulans through a simple and versatile PCR based approach. PLoS One. 2013 Aug 23;8(8):e72871. doi: 10.1371/journal.pone.0072871. eCollection , 2013. PMID:24009710 doi:http://dx.doi.org/10.1371/journal.pone.0072871
6. ↑ Fujii I, Ebizuka Y, Sankawa U. A novel anthraquinone ring cleavage enzyme from Aspergillus terreus. J Biochem. 1988 May;103(5):878-83. doi: 10.1093/oxfordjournals.jbchem.a122365. PMID:3182756 doi:http://dx.doi.org/10.1093/oxfordjournals.jbchem.a122365
7. ↑ Huang KX, Fujii I, Ebizuka Y, Gomi K, Sankawa U. Molecular cloning and heterologous expression of the gene encoding dihydrogeodin oxidase, a multicopper blue enzyme from Aspergillus terreus. J Biol Chem. 1995 Sep 15;270(37):21495-502. doi: 10.1074/jbc.270.37.21495. PMID:7665560 doi:http://dx.doi.org/10.1074/jbc.270.37.21495