7OUD

Crystal structure of a ternary complex of the flavoprotein monooxygenase GrhO5 with FAD and collinone

This is a non-PDB format compatible entry.

Summary for 7OUD

• Entry DOI: 10.2210/pdb7oud/pdb
• Related: 7OUC
• Descriptor: FAD-dependent monooxygenase GrhO5, FLAVIN-ADENINE DINUCLEOTIDE, Collinone, ... (4 entities in total)
• Functional Keywords: flavoprotein, monooxygenase, griseorhodin a biosynthesis, rubromycin biosynthesis
• Biological source: Streptomyces sp. JP95
• Total number of polymer chains: 1
• Total formula weight: 57438.55

Authors

Saleem-Batcha, R.,Toplak, M.,Teufel, R. (deposition date: 2021-06-11, release date: 2021-11-03, Last modification date: 2024-05-01)

Primary citation

Toplak, M.,Saleem-Batcha, R.,Piel, J.,Teufel, R.
Catalytic Control of Spiroketal Formation in Rubromycin Polyketide Biosynthesis.
Angew.Chem.Int.Ed.Engl., 60:26960-26970, 2021

PubMed Abstract: The medically important bacterial aromatic polyketide natural products typically feature a planar, polycyclic core structure. An exception is found for the rubromycins, whose backbones are disrupted by a bisbenzannulated [5,6]-spiroketal pharmacophore that was recently shown to be assembled by flavin-dependent enzymes. In particular, a flavoprotein monooxygenase proved critical for the drastic oxidative rearrangement of a pentangular precursor and the installment of an intermediate [6,6]-spiroketal moiety. Here we provide structural and mechanistic insights into the control of catalysis by this spiroketal synthase, which fulfills several important functions as reductase, monooxygenase, and presumably oxidase. The enzyme hereby tightly controls the redox state of the substrate to counteract shunt product formation, while also steering the cleavage of three carbon-carbon bonds. Our work illustrates an exceptional strategy for the biosynthesis of stable chroman spiroketals.

PubMed: 34652045
DOI: 10.1002/anie.202109384

Experimental method

X-RAY DIFFRACTION (2.3 Å)