Origin of Life: Can Peptides Form Naturally in Water?
Another Attempt to Leap Over an Origin-of-Life Hurdle Falls Flat
by Ross Anderson, Ph.D.
Well, here they go again, trying desperately to provide a glimmer of hope to those who insist that life arose by lifeless processes. Three evolutionists are proposing that you can get polypeptides to form in water without intelligent design. Their new proposal has been published in Nature.
An essential part of the evolutionary hypothesis is that life allegedly arose in the ocean, in what is sometimes referred to as the “prebiotic soup.” The major problem is that, until now, no one could explain how polymers of amino acids or other biomolecules could form in the presence of water. In the cell, amino acids are polymerized by molecular machines that can deal with the loss of a molecule of water for each peptide bond formed. Outside a cell, though, if the concentration of water is high, such as in the ocean, the reverse reaction would be favored; i.e., breaking peptide bonds is greatly favored over peptide bond formation. As a consequence, several investigators have proposed other scenarios where the water problem would be avoided, but all of these scenarios are not without their own problems.
Ideology Driving the Experimentation
It must be borne in mind that all hypotheses as to the abiogenetic origins of life are based on the philosophical ideology that there is no Creator, or that, if there is one, he is not involved and thus had no hand in the process. Consequently, evolutionists depend on their creative imaginations to speculate as to how life may have originated from non-life. Mind you, this is in spite of experiments done long ago by Louis Pasteur and others who demonstrated that life only originates from life. Such speculations also have to propose that the laws of thermodynamics didn’t apply at the beginning.
As with virtually all attempts to show that life could have arisen abiogenetically—no intelligence involved—there is a considerable amount of intelligence used to develop the scenario proposed here. What makes this proposal unique is that it examines a means whereby polymerization of amino acids can occur in the presence of water.
Here are the details. The series of reactions proposed by these authors consists of three reactions, what they refer to as the “ligation cycle.” It starts with a thiolysis reaction followed by a hydrolysis reaction. The authors start with a short N-acetylated peptide with a nitrile function on the C-terminus. Hydrogen sulfide (H2S) is used to displace the nitrile group from the N-acetyled peptide and, in the presence of water, generate an aminoacylthioacid. This thioacid is then set for the third reaction, an oxidation reaction, whereby the thioacid function is replaced by a nitrile derivative of an amino acid (aminonitrile); the next amino acid is ligated onto the C-terminus of the acetylated peptide. The peptide is thus extended by one amino acid and possess a nitrile function and activated for the next round of reactions.
And yet these reactions will not spontaneously occur without copious amounts of investigator interference (i.e., intelligent design by lab workers pushing results in non-natural directions). Some examples of significant investigator input are as follows:
First, all polymerization reactions in the cell require that the monomers being polymerized first be activated. In the case of protein synthesis, each amino acid is activated by attachment to a tRNA [transfer RNA]. The authors postulate some molecules could have been available in the prebiotic soup, such as ferricyanide, H2S, thioacetate, and cyanoacetylene. From that assumption, the authors concluded that formation of aminonitriles (amino acids with a nitrile function in place of the α-carboxyl group, AA-CN) would be likely. However, it was known that these do not lend themselves to efficient ligation or polymerization. They figured that if they could convert the AA-CN to an aminothioacid (AA-SH) which is stable and soluble in water, polymerization/ligation efficiency might be improved. The thiolysis and the hydrolysis reactions were shown to efficiently convert an AA-CN to an AA-SH. This, in turn, could participate in efficient ligation/polymerization of the next AA-CN to the C-terminus, and at the same time activate the -CN moiety for the next series of reactions in the cycle. [Note: moiety refers to an indefinite portion or share.]
Second, the authors found that they first had to modify the peptide with an acetyl group on the N-terminus for several reasons: (1) Without the acetyl group, they were not able to observe the generation of the aminoacylthioacid by the hydrolysis reaction, and thus no ligation would be observed. (2) Without an N-acetyl group on the N-terminus of the growing peptide, it would be progressively destroyed by the activating agent diketopiperazine (DKP). (3) Addition of the acetyl group to the α-amino group of the peptide helped to activate the nitrile moiety making it amenable to thiolysis by H2S.
Third, the authors start with short, pre-formed acetylated-peptides of glycine (Ac-Gly1-6-CN) to which they investigated the ligation of single aminonitriles, or pre-formed tripeptides. The amino acids used were all purified L-amino acids which doesn’t reflect the prebiotic soup conditions where a racemic mixture of both D- and L-amino acids would have existed. Unfortunately, the authors didn’t appear to investigate whether there is a limit to the iterative ligations after which yield drops significantly. This is important because the average number of amino acids in proteins today is 400-450 amino acids, with many being much longer. To get around this, some speculate that the first proteins were smaller; again, this is pure speculation. If that were the case, then what would be the advantage of making larger, more complex proteins?
Fourth, the authors used ferricyanide to add the nitrile moiety to the amino acids, however, both ferricyanide and H2S are highly reactive toward each other, thus they had to be added in separate, sequential steps to achieve the results reported. Of course, in the prebiotic soup these two reagents would have been mixed together, thus compromising the results reported here.
Getting the Sequence Right
As one can see, there was significant investigator involvement. Even if there wasn’t, this would not prove evolution. In all proteins there is information contained within the specific amino acid sequence, and this information is contained in the nucleic acid, DNA. It’s not enough to propose a scheme that may provide some plausible means for the abiotic synthesis of peptides. The scheme must have a way of specifying the sequence. It is the specific amino acid sequence that determines the 3-D conformation and thus function of a protein. One has to be mindful that the specific amino acid sequence in these experiments is determined by the investigators— not nature.
The authors believe their work can inform theories about the origin of life:
Amide bond formation is one of the most important reactions in both chemistry and biology, but there is currently no chemical method of achieving α-peptide ligation in water that tolerates all of the 20 proteinogenic amino acids at the peptide ligation site. The universal genetic code establishes that the biological role of peptides predates life’s last universal common ancestor and that peptides played an essential part in the origins of life.
They conclude with sheer speculation that blind nature learned how to control metabolic reactions:
Controlled synthesis, which responds to environmental or internal stimuli, is an essential element of metabolic regulation, and we speculate that coupling iterative aminonitrile ligation to metabolic (redox) cycles may lead to positive cooperative feedback during the early evolution of life.
As we have shown, however, the investigators used design to push reactions against natural tendencies. Nature is the opposite of “controlled synthesis.”
Rescuing Something Useful for Designers
While this paper really does nothing to further evolution, it does have some significance for researchers who need to make short, synthetic peptides for use in their research. To date, the “enemy” is water; all synthesis reactions have to be carried out under anhydrous [dry] conditions. Additionally, the amino acids used must have various blocking groups added to functional groups to prevent their reaction. For example, lysine has two amino groups, but only one of them (the α-amino group) is involved in peptide bond formation in proteins. The other amino group (the ε-amino group) must be prevented from participating in bond formation. Thus, it must be blocked by another moiety that can be readily removed later.
The scheme reported here can permit synthesis of peptides in the presence of water, and no added blocking groups are needed. Additionally, the reaction scheme reported here also preserves the chirality, or handedness, of the ligated amino acids. Finally, these reactions may be carried out at various temperature and pH values with good yields. Thus, this report may significantly change the way small peptides are synthesized in the lab.
It would also be interesting to investigate whether the polymerization of nucleotides into nucleic acids, like DNA and RNA, can occur under the conditions reported here. As long as materialistic ideology is not pushing the conclusions beyond what the facts warrant, and as long as results are not made to imply that nature can synthesize the “building blocks of life” blindly, or claim that this is how life started without a Creator, then the paper has some useful ideas for scientists using intelligence to build molecules by design.
Canavelli et al., “Peptide ligation by chemoselective aminonitrile coupling in water,” Nature 10 July 2019. https://www.nature.com/articles/s41586-019-1371-4
Ross Anderson (PhD, biochemistry) is professor of biochemistry at The Master’s University in southern California. Dr Anderson’s expertise is in the area of biochemistry and molecular biology. He has taught Biochemistry and helped to direct research projects of graduate and medical students at Baylor College of Medicine, Houston, TX. Dr. Anderson was a post-doctoral researcher Houston Neurosensory Center, and was a member of both the undergraduate and graduate faculty at Lamar University, Beaumont, TX. Dr Anderson’s research interests include structure-function studies of DNA polymerizing enzymes and the synthesis and expression of synthetic human genes in bacterial hosts. He has authored or co-authored several publications in major, peer-reviewed journals. He is a member of the American Chemical Society and Sigma Xi Research Society.