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Crystal structure of the bi‐functional quinone reductase/ O‐methyl transferase GilM from the gilvocarcin biosynthetic pathway (584.6)
Author(s) -
Downey Theresa,
Tibrewal Nidhi,
Tsodikov Oleg,
Rohr Jurgen
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.584.6
Subject(s) - hydroquinone , polyketide , quinone , reductase , enzyme , stereochemistry , biosynthesis , transferase , chemistry , methylation , catalytic cycle , oxidoreductase , streptomyces , biochemistry , biology , bacteria , gene , genetics
Gilvocarcin V, produced by Streptomyces griseoflavus and various other Streptomyces strains, shows significant antitumor activity and remarkably low toxicity. The enzyme GilM a pivotal enzyme in the gilvocarcin biosynthetic pathway exhibits dual functionality in that it catalyzes a reduction of a quinone intermediate to a hydroquinone and an O‐methylation. GilM mediates its reductive catalysis through the aid of GilR that provides FADH 2 for the GilM reaction, through which FAD is regenerated for the next catalytic cycle. This unusual synergy eventually completes the biosynthesis of the polyketide‐derived defuco‐gilvocarcin chromphore. Here we report the X‐ray crystal structure of GilM along with insights into its dual functionality and its interaction with the partner enzyme GilR.