A Hypothesis on the Primordial Selection of Terpenoids as Hydrophobic Biomolecules

Dear Editor:

The birth of life in the early Earth is one of mysteries. Although many studies have shown that biomolecules may have been formed abiotically, the mystery is still unsolved. Recently, we proposed two scenarios for the prebiotic route to the proteinogenic amino acids; the aminomalononitrile scenario and the new polyglycine scenario. ¹ Both scenarios involve the alkylation of the body precursor with each side-chain precursor, by which we could explain why the number of proteinogenic amino acids is limited to 20. Here we propose a parallel scenario on terpenoids, which are believed to have been generated before the last universal common ancestor (LUCA). ² Hydrophobic chains in archaeal membranes are mostly composed of terpenoids. The basic compounds are isoprenol and prenol, which have been shown to be produced abiotically from methylpropene and formaldehyde (Scheme 1). ³ Both isoprenol and prenol are closely related to the building blocks of terpenoids found in the present life.

Scheme 1.

Prebiotic Formation of Isoprenol and Prenol from Methylpropene.

In the previous scenario on amino acids, ¹ alkenes are the precursors of aliphatic amino acids; namely, propene for valine, 1- and 2-butene (E/Z) for isoleucine, and methylpropene for leucine. If these alkenes were “equally” rich in the early atmosphere, why only methylpropene was chosen as the precursor of terpenoids? The answer to this question can be explained by the stability of the intermediate carbocation. As shown in Scheme 1, methylpropene affords tert-carbocation under acidic conditions, while, in contrast, propene, 1-butene, and 2-butene generate only sec-carbocations (Scheme 2). Therefore, it appears that 3-methylbutan-1-ol derivatives (from methylpropene) accumulated more than linear compounds (from propene and 1-butene) or positional isomers (from 2-butene). This scenario has no inconsistency with the hypothesis on the primordial synthesis of the 20 amino acids. ¹

Scheme 2.

Reaction of Alkenic Compounds with Formaldehyde.

Simple alkenes are the key compounds for both amino acids and terpenoids. Formation of alkenic compounds from gas molecules, mostly from methane, has experimentally been demonstrated. ⁴ It has been shown that unsaturated hydrocarbon generates more than the corresponding saturated compounds by electric discharge. ⁵ Probably, various hydrocarbons larger than methane were also present because not only methane but also ethane are found in Titan. ⁴ We believe that various alkenic compounds were continuously generated in the primordial atmosphere.

Condensation of three molecules of acetic acid in place of acetyl CoA of the present life (the mevalonate pathway) is another possible route to terpenoids. However, because this is not an easy reaction, it is not clear whether the mevalonate pathway is another prebiotic route or was established after the birth of LUCA.

The next stage of the terpenoid synthesis includes the formation of geraniol and longer derivatives from isoprenol and prenol. The most probable route is similar to modern organisms (Scheme 3). Again, the reaction direction is the formation of more stable carbocation. Prenol affords allylic carbocation while isoprenol does not. Further reaction with isoprenol affords sesquiterpene, diterpene, and longer compounds, as in the case of the present life. Reaction with glycerol, instead of isoprenol, may be a possible route to membrane molecules. Subsequent reduction of the double bonds generates the hydrocarbon part of archaeal membrane. Formic acid is a plausible reducing agent (Scheme 4) which is a product from HCN or CO in water.

Scheme 3.

Formation of Geraniol from Prenol and Isoprenol.

Scheme 4.

Reduction of Double Bond by Formic Acid.

It is no doubt that many other hydrophobic compounds were present in the early Earth, although terpenoids were the major. For example, Scheme 2 reactions are less favorable but not excluded. Prebiotic synthesis of various hydrocarbons, not only alkenes but also alkanes and alkynes, have experimentally been evidenced.^4,5 These complex hydrophobic compounds form aggregates in water, although their structures are far from cell. The next stage is the formation of membrane molecules. Probably, terpenoids were selected from the aggregate due to their abundance. Terpenoids, especially C₁₅ and C₂₀, are the major hydrocarbon units of archaeal membranes.^2,3 As previously described, ¹ we believe that the process from simple gas molecules to biomolecules consists of three stages, fast high-energy reactions, chemo-selective organic reactions, and the combination of the unit molecules. All organic reactions for both amino acids ¹ and terpenoids (Schemes 1-4) occur under acidic conditions. The aqueous media of the early Earth is thought to have been acidic. ⁶ This is a part of evolution process from Garakuta molecules^7,8 to biomolecules.