fluorinase

Fluorinase is a bacterial enzyme originally identified in Streptomyces cattleya. It catalyzes the formation of a carbon–fluorine bond by reacting fluoride ion with S-adenosyl-L-methionine (SAM) to produce 5'-fluoro-5'-deoxyadenosine (FDA) and L-methionine. This reaction is notable because it represents one of the few known biological routes to C–F bond formation under physiological conditions and provides a basis for the microbial production of fluorinated metabolites such as fluoroacetate.

Mechanism and active site: The fluoride ion acts as a nucleophile, attacking the 5' carbon of the SAM ribose in an SN2-like step that displaces the methionine moiety and yields FDA. Structural studies indicate an active-site pocket that binds the adenosyl moiety of SAM and coordinates fluoride, enabling the reaction and stabilizing key intermediates. The enzyme is typically studied in vitro with SAM and fluoride, under conditions compatible with enzyme activity.

Biological context and distribution: Fluorinase is largely associated with fluoride biosynthesis in actinomycetes such as S. cattleya. It has attracted attention as the first proven enzyme capable of forming C–F bonds in nature and as a model for understanding halogenation catalysis. The downstream metabolic fate of FDA can feed into fluorometabolite pathways that generate fluorinated compounds.

Applications and limitations: In biotechnology, fluorinase enables chemoenzymatic synthesis of fluorinated building blocks by generating FDA, which can be used in subsequent reactions to access fluorinated nucleosides and other fluorinated motifs. It also opens routes to radiolabeled fluorine-18–containing tracers. However, practical use is tempered by the enzyme's requirement for relatively high fluoride concentrations, limited substrate scope, and stability; ongoing protein engineering aims to broaden its utility.