Characterization and Crystal Structure of a Nonheme Diiron Monooxygenase Involved in Platensimycin and Platencin Biosynthesis
2019
Nonheme diiron
monooxygenasesmake up a rapidly growing family of
oxygenasesthat are rarely identified in
secondary metabolism. Herein, we report the in vivo, in vitro, and structural characterizations of a nonheme diiron
monooxygenase, PtmU3, that installs a C-5 β-hydroxyl group in the unified biosynthesis of platensimycin and platencin, two highly functionalized diterpenoids that act as potent and selective inhibitors of bacterial and mammalian
fatty acid synthases. This hydroxylation sets the stage for the subsequent A-ring cleavage step key to the unique
diterpene-derived scaffolds of platensimycin and platencin. PtmU3 adopts an unprecedented
triosephosphate isomerase(
TIM)
barrelstructural fold for this class of enzymes and possesses a noncanonical diiron active site architecture with a saturated six-coordinate iron center lacking a μ-oxo bridge. This study reveals the first member of a previously unidentified superfamily of
TIM-barrel-fold enzymes for metal-dependent dioxygen activation, with the ...
Keywords:
-
Correction
-
Source
-
Cite
-
Save
44
References
9
Citations
NaN
KQI