53825-23-3Relevant academic research and scientific papers
Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
supporting information, p. 8297 - 8302 (2021/03/01)
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
Mechanistic Investigation of a Non-Heme Iron Enzyme Catalyzed Epoxidation in (-)-4′-Methoxycyclopenin Biosynthesis
Chang, Wei-Chen,Li, Jikun,Lee, Justin L.,Cronican, Andrea A.,Guo, Yisong
, p. 10390 - 10393 (2016/09/04)
Mechanisms have been proposed for α-KG-dependent non-heme iron enzyme catalyzed oxygen atom insertion into an olefinic moiety in various natural products, but they have not been examined in detail. Using a combination of methods including transient kinetics, M?ssbauer spectroscopy, and mass spectrometry, we demonstrate that AsqJ-catalyzed (-)-4′-methoxycyclopenin formation uses a high-spin Fe(IV)-oxo intermediate to carry out epoxidation. Furthermore, product analysis on 16O/18O isotope incorporation from the reactions using the native substrate, 4′-methoxydehydrocyclopeptin, and a mechanistic probe, dehydrocyclopeptin, reveals evidence supporting oxo? hydroxo tautomerism of the Fe(IV)-oxo species in the non-heme iron enzyme catalysis.
