@article{bashiri_bulloch_bramley_davidson_stuteley_young_harris_naqvi_middleditch_schmitz_et al._2024, title={Poly-γ-glutamylation of biomolecules}, volume={15}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-024-45632-1}, abstractNote={AbstractPoly-γ-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates and F420. Despite decades of research, key mechanistic questions remain as to how enzymes successively add glutamates to poly-γ-glutamate chains while maintaining cofactor specificity. Here, we show how poly-γ-glutamylation of folate and F420 by folylpolyglutamate synthases and γ-glutamyl ligases, non-homologous enzymes, occurs via processive addition of L-glutamate onto growing γ-glutamyl chain termini. We further reveal structural snapshots of the archaeal γ-glutamyl ligase (CofE) in action, crucially including a bulged-chain product that shows how the cofactor is retained while successive glutamates are added to the chain terminus. This bulging substrate model of processive poly-γ-glutamylation by terminal extension is arguably ubiquitous in such biopolymerisation reactions, including addition to folates, and demonstrates convergent evolution in diverse species from archaea to humans.}, number={1}, journal={NATURE COMMUNICATIONS}, author={Bashiri, Ghader and Bulloch, Esther M. M. and Bramley, William R. and Davidson, Madison and Stuteley, Stephanie M. and Young, Paul G. and Harris, Paul W. R. and Naqvi, Muhammad S. H. and Middleditch, Martin J. and Schmitz, Michael and et al.}, year={2024}, month={Feb} }
 @article{cha_milikisiyants_davidson_xue_smirnova_smirnov_guo_chang_2020, title={Alternative Reactivity of Leucine 5-Hydroxylase Using an Olefin-Containing Substrate to Construct a Substituted Piperidine Ring}, volume={59}, ISSN={["0006-2960"]}, url={https://doi.org/10.1021/acs.biochem.0c00289}, DOI={10.1021/acs.biochem.0c00289}, abstractNote={Applying enzymatic reactions to produce useful molecules is a central focus of chemical biology. Iron and 2-oxoglutarate (Fe/2OG) enzymes are found in all kingdoms of life and catalyze a broad array of oxidative transformations. Herein, we demonstrate that the activity of an Fe/2OG enzyme can be redirected when changing the targeted carbon hybridization from sp3 to sp2. During leucine 5-hydroxylase catalysis, installation of an olefin group onto the substrate redirects the Fe(IV)-oxo species reactivity from hydroxylation to asymmetric epoxidation. The resulting epoxide subsequently undergoes intramolecular cyclization to form the substituted piperidine, 2S,5S-hydroxypipecolic acid.}, number={21}, journal={BIOCHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Cha, Lide and Milikisiyants, Sergey and Davidson, Madison and Xue, Shan and Smirnova, Tatyana I and Smirnov, Alex I and Guo, Yisong and Chang, Wei-Chen}, year={2020}, month={Jun}, pages={1961–1965} }
 @article{davidson_mcnamee_fan_guo_chang_2019, title={Repurposing Nonheme Iron Hydroxylases To Enable Catalytic Nitrile Installation through an Azido Group Assistance}, volume={141}, ISSN={["0002-7863"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85062294563&partnerID=MN8TOARS}, DOI={10.1021/jacs.8b13906}, abstractNote={Three mononuclear nonheme iron and 2-oxoglutarate dependent enzymes, l-Ile 4-hydroxylase, l-Leu 5-hydroxylase and polyoxin dihydroxylase, are previously reported to catalyze the hydroxylation of l-isoleucine, l-leucine, and l-α-amino-δ-carbamoylhydroxyvaleric acid (ACV). In this study, we showed that these enzymes can accommodate leucine isomers and catalyze regiospecific hydroxylation. On the basis of these results, as a proof-of-concept, we demonstrated that the outcome of the reaction can be redirected by installation of an assisting group within the substrate. Specifically, instead of canonical hydroxylation, these enzymes can catalyze non-native nitrile group installation when an azido group is introduced. The reaction is likely to proceed through C-H bond activation by an Fe(IV)-oxo species, followed by azido-directed C≡N bond formation. These results offer a unique opportunity to investigate and expand the reaction repertoire of Fe/2OG enzymes.}, number={8}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Davidson, Madison and McNamee, Meredith and Fan, Ruixi and Guo, Yisong and Chang, Wei-chen}, year={2019}, month={Feb}, pages={3419–3423} }
 @article{liao_li_huang_davidson_kurnikov_lin_lee_kurnikova_guo_chan_et al._2018, title={Insights into the Desaturation of Cyclopeptin and its C3 Epimer Catalyzed by a non-Heme Iron Enzyme: Structural Characterization and Mechanism Elucidation}, volume={57}, ISSN={["1521-3773"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85040694556&partnerID=MN8TOARS}, DOI={10.1002/anie.201710567}, abstractNote={AbstractAsqJ, an iron(II)‐ and 2‐oxoglutarate‐dependent enzyme found in viridicatin‐type alkaloid biosynthetic pathways, catalyzes sequential desaturation and epoxidation to produce cyclopenins. Crystal structures of AsqJ bound to cyclopeptin and its C3 epimer are reported. Meanwhile, a detailed mechanistic study was carried out to decipher the desaturation mechanism. These findings suggest that a pathway involving hydrogen atom abstraction at the C10 position of the substrate by a short‐lived FeIV‐oxo species and the subsequent formation of a carbocation or a hydroxylated intermediate is preferred during AsqJ‐catalyzed desaturation.}, number={7}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Liao, Hsuan-Jen and Li, Jikun and Huang, Jhih-Liang and Davidson, Madison and Kurnikov, Igor and Lin, Te-Sheng and Lee, Justin L. and Kurnikova, Maria and Guo, Yisong and Chan, Nei-Li and et al.}, year={2018}, month={Feb}, pages={1831–1835} }