@article{li_liao_tang_huang_cha_lin_lee_kurnikov_kurnikova_chang_et al._2020, title={Epoxidation Catalyzed by the Nonheme Iron(II)- and 2-Oxoglutarate-Dependent Oxygenase, AsqJ: Mechanistic Elucidation of Oxygen Atom Transfer by a Ferryl Intermediate}, volume={142}, ISSN={["1520-5126"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85083666781&partnerID=MN8TOARS}, DOI={10.1021/jacs.0c00484}, abstractNote={Mechanisms of enzymatic epoxidation via oxygen atom transfer (OAT) to an olefin moiety is mainly derived from the studies on thiolate-heme containing epoxidases, such as cytochrome P450 epoxidases. The molecular basis of epoxidation catalyzed by non-heme-iron enzymes is much less explored. Herein, we present a detailed study on epoxidation catalyzed by the non-heme iron- and 2-oxoglutarate-dependent (Fe/2OG) oxygenase, AsqJ. The native substrate and analogs with different para substituents ranging from electron-donating groups (e.g. methoxy) to electron-withdrawing groups (e.g. trifluoromethyl) were used to probe the mechanism. The results derived from transient-state enzyme kinetics, Mössbauer spectroscopy, reaction product analysis, X-ray crystallography, density functional theory calculations and molecular dynamic simulations collectively revealed the following mechanistic insights: 1) The rapid O2 addition to the AsqJ Fe(II) center occurs with the iron-bound 2OG adopting an online-binding mode in which the C1 carboxylate group of 2OG is trans to the proximal histidine (His134) of the 2-His-1-carboxylate facial triad, instead of assuming the offline-binding mode with the C1 carboxylate group trans to the distal histidine (His211); 2) The decay rate constant of the ferryl intermediate is not strongly affected by the nature of the para substituents of the substrate during the OAT step, a reactivity behavior that is drastically different from non-heme Fe(IV)-oxo synthetic model complexes; 3) The OAT step most likely proceeds through a step-wise process with the initial formation of C(benzylic)-O bond to generate an Fe(III)-alkoxide species, which is observed in the AsqJ crystal structure. The subsequent C3-O bond formation completes the epoxide installation.}, number={13}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Li, Jikun and Liao, Hsuan-Jen and Tang, Yijie and Huang, Jhih-Liang and Cha, Lide and Lin, Te-Sheng and Lee, Justin L. and Kurnikov, Igor V and Kurnikova, Maria G. and Chang, Wei-Chen and et al.}, year={2020}, month={Apr}, pages={6268–6284} }
 @article{chang_sanyal_huang_ittiamornkui_zhu_liu_2017, title={In Vitro Stepwise Reconstitution of Amino Acid Derived Vinyl Isocyanide Biosynthesis: Detection of an Elusive Intermediate}, volume={19}, ISSN={["1523-7052"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85014520010&partnerID=MN8TOARS}, DOI={10.1021/acs.orglett.7b00258}, abstractNote={In vitro reconstitution of a newly discovered isonitrile synthase (AmbI1 and AmbI2) and the detection of an elusive intermediate (S)-3-(1H-indol-3-yl)-2-isocyanopropanoic acid 1 in indolyl vinyl isocyanide biogenesis are reported. The characterization of iron/2-oxoglutarate (Fe/2OG) dependent desaturases IsnB and AmbI3 sheds light on the possible mechanism underlying stereoselective alkene installation to complete the biosynthesis of (E)- and (Z)-3-(2-isocyanovinyl)-1H-indole 2 and 5. Establishment of a tractable isonitrile synthase system (AmbI1 and AmbI2) paves the way to elucidate the enigmatic enzyme mechanism for isocyanide formation.}, number={5}, journal={ORGANIC LETTERS}, author={Chang, Wei-Chen and Sanyal, Dev and Huang, Jhih-Liang and Ittiamornkui, Kuljira and Zhu, Qin and Liu, Xinyu}, year={2017}, month={Mar}, pages={1208–1211} }