7wh9
holo structure of emodin 1-OH O-methyltransferase complex with emodin and S-Adenosyl-L-homocysteine
Structural highlights
FunctionGEDA_ASPTN O-methyltransferase; part of the gene cluster that mediates the biosynthesis of geodin, an intermediate in the biosynthesis of other natural products (PubMed:19549600, PubMed:24009710, PubMed:7665560). 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] Publication Abstract from PubMedAll O-methylated derivatives of emodin, including physcion, questin, and 1-O-methylemodin, show potential antifungal activities. Notably, emodin and questin are two pivotal intermediates of geodin biosynthesis in Aspergillus terreus. Although most of the geodin biosynthetic steps have been investigated, the key O-methyltransferase (OMT) responsible for the O-methylation of emodin to generate questin has remained unidentified. Herein, through phylogenetic tree analysis and in vitro biochemical assays, the long-sought class II emodin-O-methyltransferase GedA has been functionally characterized. Additionally, the catalytic mechanism and key residues at the catalytic site of GedA were elucidated by enzyme-substrate-methyl donor analogue ternary complex crystal structure determination and site-directed mutagenesis. As we demonstrate, GedA adopts a typical general acid/base (E446/H373)-mediated transmethylation mechanism. In particular, residue D374 is also crucial for efficient catalysis through blocking the formation of intramolecular hydrogen bonds in emodin. This study will facilitate future engineering of GedA for the production of physcion or other site-specific O-methylated anthraquinone derivatives with potential applications as biopesticides. Characterization and Structural Analysis of Emodin-O-Methyltransferase from Aspergillus terreus.,Xue Y, Liang Y, Zhang W, Geng C, Feng D, Huang X, Dong S, Zhang Y, Sun J, Qi F, Lu X J Agric Food Chem. 2022 May 11;70(18):5728-5737. doi: 10.1021/acs.jafc.2c01281. , Epub 2022 Apr 27. PMID:35475366[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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