title: Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse.
abstract: Naturally produced halogenated compounds are ubiquitous across all domains of life where they perform a multitude of biological functions and adopt a diversity of chemical structures. Accordingly, a diverse collection of enzyme catalysts to install and remove halogens from organic scaffolds has evolved in nature. Accounting for the different chemical properties of the four halogen atoms (fluorine, chlorine, bromine, and iodine) and the diversity and chemical reactivity of their organic substrates, enzymes performing biosynthetic and degradative halogenation chemistry utilize numerous mechanistic strategies involving oxidation, reduction, and substitution. Biosynthetic halogenation reactions range from simple aromatic substitutions to stereoselective C-H functionalizations on remote carbon centers and can initiate the formation of simple to complex ring structures. Dehalogenating enzymes, on the other hand, are best known for removing halogen atoms from man-made organohalogens, yet also function naturally, albeit rarely, in metabolic pathways. This review details the scope and mechanism of nature's halogenation and dehalogenation enzymatic strategies, highlights gaps in our understanding, and posits where new advances in the field might arise in the near future.
authors.affiliation: Center for Oceans and Human Health, Scripps Institution of Oceanography, University of California San Diego , La Jolla, California 92093, United States.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Agarwal
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego , La Jolla, California 92093, United States.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Miles
authors.affiliation: Department of Medicinal Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Winter
authors.affiliation: College of Pharmacy, Department of Medicinal Chemistry & Pharmacognosy and Center for Biomolecular Sciences, University of Illinois at Chicago , Chicago, Illinois 60612, United States.
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Eustáquio
authors.affiliation: Center for Oceans and Human Health, Scripps Institution of Oceanography, University of California San Diego , La Jolla, California 92093, United States.
authors.forename: Abrahim A
authors.initials: AA
authors.lastname: El Gamal
authors.affiliation: Center for Oceans and Human Health, Scripps Institution of Oceanography, University of California San Diego , La Jolla, California 92093, United States.|Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego , La Jolla, California 92093, United States.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, California 92093, United States.
authors.forename: Bradley S
authors.identifier: http://orcid.org/0000-0002-4652-1253
authors.initials: BS
authors.lastname: Moore
mesh_terms: D004798:Enzymes / Q000737:chemistry*; D005415:Flavins / Q000737:chemistry; D006219:Halogens / Q000737:chemistry*; D014639:Vanadium / Q000737:chemistry
chemical_list: D004798:Enzymes; D005415:Flavins; D006219:Halogens; D014639:Vanadium