Enzymatic fluorination and biotechnological development of the fluorinase

David O'Hagan (Corresponding Author), Hai Deng (Corresponding Author)

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123 Citations (Scopus)

Abstract

Despite a long and distinguished history focused on the isolation and structural elucidation of secondary metabolites from all classes of organisms, organic chemists have only securely identified five unique fluorine-containing metabolites from an estimated 130 000 structurally characterized natural
products (see Figure 1). This absence of fluorometabolites in our natural product inventory arises for several reasons. Fluoride ion has very low abundance (F− = 1.3 ppm) in the oceans relative to chloride (Cl− = 20 000 ppm) and bromide
(Br− = 70 ppm), and thus its bioavailability is low. It also has the highest heat of hydration (∼120 kcal mol−1); therefore, to achieve nucleophilic catalysis from water, an enzyme has to evolve a desolvation strategy. Much of the biochemistry of the other halogens involves the oxidation of halide ions (X−) to halonium ions (X+) or halide radicals (X·), but the high electronegativity of fluorine mitigates against an oxidation approach. It is interesting that iodide, which is even less
abundant than fluoride in surface water (F− = 1.3 ppm vs I− = 0.02 ppm), has given rise to ∼120 iodine-containing natural products. This is because iodide, unlike fluoride, is readily oxidized by haloperoxidases, and it finds an entry into
enzymology through the relative ease of iodonium ion (I+) generation. The haloperoxidases do not oxidize F− because the oxidation potential of hydrogen peroxide (−1.8 eV) is above that of fluoride (F− = −2.87 eV) but lower than that of the other halogens (Cl− = −1.36 eV; Br− = −1.07 ev; I− = −0.54ev). Thus, the physical properties of fluoride appear to have limited the evolution of fluorine biochemistry. However, nature has found a way, and a few rare fluorometabolites have been identified, as illustrated in Figure 1. The most ubiquitious metabolite is fluoroacetate 1, which was first identified from
Dichapetalum cymosum in South Africa but has been subsequently found in a variety of plants across the globe, particularly in southern and tropical regions of Africa, Australia, and Brazil
Original languageEnglish
Pages (from-to)634-649
Number of pages16
JournalChemical Reviews
Volume115
Issue number2
Early online date25 Sep 2014
DOIs
Publication statusPublished - 28 Jan 2015

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Keywords

  • Enzymatic Fluorination
  • Biotechnological Developments

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