Reasons why life on Earth rarely makes fluorine-containing compounds and their implications for the search for life beyond Earth

Abstract

Life on Earth is known to rarely make fluorinated carbon compounds, as compared to other halocarbons. We quantify this rarity, based on our exhaustive natural products database curated from available literature. We build on explanations for the scarcity of fluorine chemistry in life on Earth, namely that the exclusion of the C-F bond stems from the unique physico-chemical properties of fluorine, predominantly its extreme electronegativity and strong hydration shell. We further show that the C-F bond is very hard to synthesize and when it is made by life its potential biological functions can be readily provided by alternative functional groups that are much less costly to incorporate into existing biochemistry. As a result, the overall evolutionary cost-to-benefit balance of incorporation of the C-F bond into the chemical repertoire of life is not favorable. We argue that the limitations of organofluorine chemistry are likely universal in that they do not exclusively apply to specifics of Earth's biochemistry. C-F bonds, therefore, will be rare in life beyond Earth no matter its chemical makeup.

Figure 1

Elemental abundances amongst natural products (NPs). The number of natural products in our database containing a given element and the percentage number are shown. The halogen atoms Cl- and Br-containing compounds are nearly as common as S–containing compounds amongst natural products. In contrary to Cl, Br and even I halogens, F-containing natural compounds are severely underrepresented in the chemical repertoire of life on Earth. The figure compilation shows only elements that can form covalent bonds that are stable in water. The compilation excludes transition metals from the analysis. (*) No molecules containing Si bonded to any atom other than oxygen are known to be made by life, although silica and silicic acid are used extensively by life on Earth.

Figure 2

Abundance of chemical bonds containing halogens (F, Cl, Br, I) and biogenic elements (C, O, N, S, P) among natural products (NPs). The figure depicts the number of natural products in our database containing chemical bonds with halogen atoms and the percentage number of all natural products containing these chemical bonds. The numbers show that not all bonds between halogen atoms and the five biogenic elements are equally frequent amongst natural products, some bonds are more common (C–Cl, C–Br, C–I) than others (C–F, N–Br) and some are very rare in Earth’s biochemistry.

Figure 3

Biosynthesis of C–F bonds. The first native fluorinase that has been characterized is a nucleophilic halogenase, flA from Streptomyces cattleya. The fluorinase flA, isolated from S. cattleya in 2002, catalyses C–F bond formation from an inorganic fluoride ion. FlA fluorinase mediates a reaction between S-adenosyl-L-methionine (SAM) and a fluoride ion to yield 5’-fluorodeoxyadenosine (22) and L-methionine, the first step in the biosynthesis of fluoroacetate (16) and 4-fluorothreonine (18). SAM S-adenosyl-L-methionine, Met L-methionine, Pi phosphate, DHAP dihydroxyacetone phosphate, NADH/NAD⁺: reduced and oxidized variants of nicotinamide adenine dinucleotide, FlA: Fluorinase, FlB 5′-fluoro-5′-deoxyadenosine phosphorylase, FDRI 5-fluoro-5-deoxyribose-1-phosphate isomerase, FAlDH fluoroacetaldehyde dehydrogenase, FT transaldolase fluorothreonine transaldolase. *putative aldolase responsible for the formation of fluoroacetalaldehyde (15). Figure modified and adapted from.

Figure 4

Production of toxic fluorocitrate (20) inhibitor of the tricarboxylic acid cycle (TCA). Upper panel: TCA cycle generating cis-aconitate through the action of the enzyme aconitate hydratase; lower panel: inhibition of aconitate hydratase as a result of fluorocitrate production. Figure adapted and modified from:.