Although fluorine in the form of fluoride minerals is the most abundant halogen in the Earth's crust, only 12 naturally occurring organofluorine compounds have so far been found¹, and how these are biosynthesized remains a mystery². Here we describe an enzymatic reaction that occurs in the bacterium Streptomyces cattleya and which catalyses the conversion of fluoride ion and S-adenosylmethionine (SAM) to 5′-fluoro-5′-deoxyfluoroadenosine (5′-FDA). To our knowledge, this is the first fluorinase enzyme to be identified, a discovery that opens up a new biotechnological opportunity for the preparation of organofluorine compounds.

Fungi have been extensively studied for their capacity to biotransform a wide range of natural and xenobiotic compounds. This versatility is a reflection of the broad substrate specificity of fungal enzymes such as laccases, peroxidases and cytochromes P450, which are involved in these reactions. This review gives an account of recent advances in the understanding of fungal metabolism of drugs and pollutants such as dyes, agrochemicals and per- and poly-fluorinated alkyl substances (PFAS), and describes the key enzymes involved in xenobiotic biotransformation. The potential of fungi and their enzymes in the bioremediation of polluted environments and in the biocatalytic production of important compounds is also discussed.

We previously reviewed the use of ¹⁹F NMR in the broad field of chemical biology [Cobb, S. L.; Murphy, C. D. J. Fluorine Chem. 2009, 130, 132–140] and present here a summary of the literature from the last decade that has the technique as the central method of analysis. The topics covered include the synthesis of new fluorinated probes and their incorporation into macromolecules, the application of ¹⁹F NMR to monitor protein–protein interactions, protein–ligand interactions, physiologically relevant ions and in the structural analysis of proteins and nucleic acids. The continued relevance of the technique to investigate biosynthesis and biodegradation of fluorinated organic compounds is also described.

Fluorine's unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the physicochemical characteristics of the element. Examples of more recently used larger scale synthetic methods for introduction of fluorine into drug leads are detailed and the potential for using biological systems for fluorinated drug production is discussed. The synthetic procedures for carbon-fluorine bond formation largely still rely on decades-old technology for the manufacturing scale and new reagents and methods are required to meet the demands for the preparation of structurally more complex drugs. The improvement of in vitro and computational methods should make fluorinated drug design more efficient and place less emphasis on approaches such as fluorine scanning and animal studies. The introduction of new fluorinated drugs, and in particular those that have novel fluorinated functional groups, should be accompanied by rigorous environmental assessment to determine the nature of transformation products that may cause ecological damage.