Journal ArticleDOI
Aminoperoxide adducts expand the catalytic repertoire of flavin monooxygenases.
Arne Matthews,Raspudin Saleem-Batcha,Jacob N. Sanders,Frederick Stull,K. N. Houk,Robin Teufel +5 more
Reads0
Chats0
TLDR
It is demonstrated that overlooked flavin-N5-oxygen adducts are more widespread and may facilitate versatile chemistry, thus upending the notion that flavin monooxygenases exclusively function as nature’s equivalents to organic peroxides in synthetic chemistry.Abstract:
One of the hallmark reactions catalyzed by flavin-dependent enzymes is the incorporation of an oxygen atom derived from dioxygen into organic substrates. For many decades, these flavin monooxygenases were assumed to use exclusively the flavin-C4a-(hydro)peroxide as their oxygen-transferring intermediate. We demonstrate that flavoenzymes may instead employ a flavin-N5-peroxide as a soft α-nucleophile for catalysis, which enables chemistry not accessible to canonical monooxygenases. This includes, for example, the redox-neutral cleavage of carbon-hetero bonds or the dehalogenation of inert environmental pollutants via atypical oxygenations. We furthermore identify a shared structural motif for dioxygen activation and N5-functionalization, suggesting a conserved pathway that may be operative in numerous characterized and uncharacterized flavoenzymes from diverse organisms. Our findings show that overlooked flavin-N5-oxygen adducts are more widespread and may facilitate versatile chemistry, thus upending the notion that flavin monooxygenases exclusively function as nature's equivalents to organic peroxides in synthetic chemistry.read more
Citations
More filters
Journal ArticleDOI
Flavoprotein monooxygenases: Versatile biocatalysts.
TL;DR: Flavoprotein monooxygenases (FPMOs) are single or two-component enzymes that catalyze a diverse set of chemo-, regio-and enantioselective oxyfunctionalization reactions as mentioned in this paper.
Journal ArticleDOI
Enzymatic Hydroxylations of sp3-Carbons
Journal ArticleDOI
The devil is in the details: The chemical basis and mechanistic versatility of flavoprotein monooxygenases
TL;DR: In this paper, the structural and mechanistic characteristics of distinct types of flavoprotein monooxygenases (FPMOs) are highlighted, which enables reactions such as (aromatic) hydroxylation, epoxidation, (de)halogenation, heteroatom oxygenation, Baeyer-Villiger oxidation, or non-oxidative carbon-hetero bond cleavage.
Journal ArticleDOI
Oxidative Carbon Backbone Rearrangement in Rishirilide Biosynthesis.
Olga Tsypik,Roman Makitrynskyy,Britta Frensch,David L. Zechel,Thomas Paululat,Robin Teufel,Andreas Bechthold +6 more
TL;DR: In conclusion, gene deletion experiments and in vitro enzyme studies are employed to identify key biosynthetic intermediates and expose intricate redox tailoring steps for the formation of rishirilide A, B, and D and lupinacidin A.
Journal ArticleDOI
Enzymatic spiroketal formation via oxidative rearrangement of pentangular polyketides.
Britta Frensch,Thorsten Lechtenberg,Michel Kather,Zeynep Yunt,Martin U. Betschart,Bernd Kammerer,Steffen Lüdeke,Michael Müller,Jörn Piel,Robin Teufel +9 more
TL;DR: In this article, a polycyclic aromatic precursor undergoes extensive enzymatic oxidative rearrangement catalyzed by two flavoprotein monooxygenases and a flavouroprotein oxidase that ultimately results in a drastic distortion of the carbon skeleton.
References
More filters
Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
Journal ArticleDOI
The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals
Yan Zhao,Donald G. Truhlar +1 more
TL;DR: The M06-2X meta-exchange correlation function is proposed in this paper, which is parametrized including both transition metals and nonmetals, and is a high-non-locality functional with double the amount of nonlocal exchange.
Journal ArticleDOI
AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading
Oleg Trott,Arthur J. Olson +1 more
TL;DR: AutoDock Vina achieves an approximately two orders of magnitude speed‐up compared with the molecular docking software previously developed in the lab, while also significantly improving the accuracy of the binding mode predictions, judging by tests on the training set used in AutoDock 4 development.
Journal ArticleDOI
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Journal ArticleDOI
Phaser crystallographic software
Airlie J. McCoy,Ralf W. Grosse-Kunstleve,Paul D. Adams,Martyn Winn,Laurent C. Storoni,Randy J. Read +5 more
TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.