Yaoyao Shen, Anyi Sun, Yisong Guo* and Wei-chen Chang*,
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Discovery of Noncanonical Iron and 2-Oxoglutarate Dependent Enzymes Involved in C–C and C–N Bond Formation in Biosynthetic Pathways
Iron and 2-oxoglutarate dependent (Fe/2OG) enzymes utilize an FeIV═O species to catalyze the functionalization of otherwise chemically inert C–H bonds. In addition to the more familiar canonical reactions of hydroxylation and chlorination, they also catalyze several other types of reactions that contribute to the diversity and complexity of natural products. In the past decade, several new Fe/2OG enzymes that catalyze C–C and C–N bond formation have been reported in the biosynthesis of structurally complex natural products. Compared with hydroxylation and chlorination, the catalytic cycles of these Fe/2OG enzymes involve distinct mechanistic features to enable noncanonical reaction outcomes. This Review summarizes recent discoveries of Fe/2OG enzymes involved in C–C and C–N bond formation with a focus on reaction mechanisms and their roles in natural product biosynthesis.
期刊介绍:
ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.