TY - JOUR
T1 - Roles of the synergistic reductive O-methyltransferase GilM and of O-methyltransferase GilMT in the gilvocarcin biosynthetic pathway
AU - Tibrewal, Nidhi
AU - Downey, Theresa E.
AU - Van Lanen, Steven G.
AU - Ul Sharif, Ehesan
AU - O'Doherty, George A.
AU - Rohr, Jürgen
PY - 2012/8/1
Y1 - 2012/8/1
N2 - Two enzymes of the gilvocarcin biosynthetic pathway, GilMT and GilM, with unclear functions were investigated by in vitro studies using purified, recombinant enzymes along with synthetically prepared intermediates. The studies revealed GilMT as a typical S-adenosylmethionine (SAM) dependent O-methyltransferase, but GilM was identified as a pivotal enzyme in the pathway that exhibits dual functionality in that it catalyzes a reduction of a quinone intermediate to a hydroquinone, which goes hand-in-hand with a stabilizing O-methylation and a hemiacetal formation. GilM mediates its reductive catalysis through the aid of GilR that provides FADH2 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.
AB - Two enzymes of the gilvocarcin biosynthetic pathway, GilMT and GilM, with unclear functions were investigated by in vitro studies using purified, recombinant enzymes along with synthetically prepared intermediates. The studies revealed GilMT as a typical S-adenosylmethionine (SAM) dependent O-methyltransferase, but GilM was identified as a pivotal enzyme in the pathway that exhibits dual functionality in that it catalyzes a reduction of a quinone intermediate to a hydroquinone, which goes hand-in-hand with a stabilizing O-methylation and a hemiacetal formation. GilM mediates its reductive catalysis through the aid of GilR that provides FADH2 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.
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U2 - 10.1021/ja305113d
DO - 10.1021/ja305113d
M3 - Article
C2 - 22800463
AN - SCOPUS:84864444670
SN - 0002-7863
VL - 134
SP - 12402
EP - 12405
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 30
ER -