Fluorinase-Enzyme Applications in Natural Product Biosynthesis

Natural enzymatic fluorination remains a singular example of nature’s ability to forge carbon–fluorine bonds under mild conditions. Central to this process is the fluorinase enzyme, which mediates the nucleophilic attack of fluoride on S-adenosyl-L-methionine to yield 5′-fluoro-5′-deoxyadenosine, a pivotal intermediate in the biosynthesis of diverse organofluorine natural products. Since the first characterised fluorinase from Streptomyces cattleya, researchers have uncovered homologues in terrestrial and marine actinomycetes, broadened substrate acceptance through site-directed mutagenesis and harnessed the enzyme in chemoenzymatic cascades. These efforts have yielded new fluorometabolites, illuminated self-protection mechanisms in producer organisms and established platforms for the synthesis of fluorinated pharmaceuticals under environmentally benign conditions. Moreover, integration of fluorinases into synthetic biology frameworks has enabled the in vivo production of novel fluorinated compounds, opening avenues for sustainable manufacturing of agrochemicals, imaging agents and therapeutic leads.

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Fluorinase-Enzyme Applications in Natural Product Biosynthesis publication trend

The graph below shows the total number of articles in fluorinase-enzyme applications in natural product biosynthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Fluorinase: Enzyme that catalyses the formation of a carbon–fluorine bond by transferring fluoride to S-adenosyl-L-methionine, producing 5′-fluoro-5′-deoxyadenosine.

S-adenosyl-L-methionine (SAM): A common methyl donor in biological systems that serves as the electrophilic substrate in fluorinase-catalysed fluorination.

Transhalogenation: Enzymatic exchange of one halogen for another on an organic substrate, exploited for radiochemical labelling.

Radiolabelling: Incorporation of a radioactive isotope—in this context fluorine-18—into a molecule for imaging or tracking in biological systems.

References

1. Biological fluorination from the sea: discovery of a SAM-dependent nucleophilic fluorinating enzyme from the marine-derived bacterium Streptomyces xinghaiensis NRRL B24674. RSC Advances (2016).
2. A two-step fluorinase enzyme mediated 18 F labelling of an RGD peptide for positron emission tomography. Chemical Communications (2015).
3. Characterization of a SAM-dependent fluorinase from a latent biosynthetic pathway for fluoroacetate and 4-fluorothreonine formation in Nocardia brasiliensis. F1000Research (2014).