A wonderful place to consider the interface of RNA catalysis and enzyme catalysis.
Sometimes I like to drift around in the scientific literature and learn about things about which I know little, or about which I haven't thought for a long time.
Many years ago - quite a long time ago - I used to play around with amino acid chemistry making some lovely messes of things as well as some very beautiful and interesting compounds that actually went commercial on a large industrial scale.
Anyway, back in the late 1980's Thomas Cech and Sidney Altman were awarded the Nobel Prize in chemistry for their discovery of the catalytic properties of RNA, which lead to much speculation about a prebiotic (or neobiotic) "RNA world" wherein life arose not as suggested in the famous Miller experiment, but rather from RNA. (It is known that the basic constituents of RNA, purines and pyrimidines, as well as some simple sugars not all that far from ribose are found in interstellar clouds.)
Over the years, I've been intrigued by origin of life and the related issue of the origin of chirality.
In my stumbles today, I came across an interesting recent review of something which I was unaware, the role of amino acid acylated tRNA in the synthesis of certain natural products with very complex structures and a wide array of precisely ordered chiral centers. (Chirality is the property of something which cannot be superimposed on its mirror image, the most convenient example being two hands on a person.)
For example, here is the structure of the natural product ergotamine, from which one can obtain (by hydrolysis) lysergic acid, the precursor of the notorious drug LSD:
If one looks at this molecule with an organic chemist's eye and one is also familiar with the twenty proteinaceous amino acids, one can see that the part of the system (the four fused ring portion that is the core of lysergic acid) can be derived from the amino acid tryptophan by self acylation of the benzo ring, followed by conversion of a resulting keto function into a double bond as part of a cyclization process, a process that one can certainly engineer relatively easily in a lab. Similarly, one can identify in the three fused ring system in the ergotamine molecule a possibly phenylalanine derived portion, a proline portion and an alanine portion. (I actually have no idea about the actual biosynthesis of this molecule.)
We see some very complex natural products of extreme importance to humanity, the total synthesis of which remains even in these times synthetically inaccessible. Examples include the core of taxanes, an important class of cancer drugs, as well as many complex antibiotics like for instance, vancomycin, which clearly involves tyrosine and phenylalanine origins:
And so it I'm wandering through this very beautiful review, which examines the role that the catalytic activity of acyl RNA plays in the biosynthesis of these important molecules: Aminoacyl-tRNA-Utilizing Enzymes in Natural Product Biosynthesis (Mireille Moutiez†, Pascal Belin†, and Muriel Gondry, Chem. Rev., 2017, 117 (8), pp 5578–5618).
The review article - which I've not finished reading yet - is very interesting, and although I don't see where it offers any speculations on the origin of life and the role of RNA in creating the protein carbohydrate world in which we now live, it thrills the imagination.
Some stuff from the introductory text:
...The enzymes of the glutamyl-tRNA reductase family reduce the aminoacyl moiety of Glu-tRNAGlu to form glutamate1-semialdehyde, the first precursor in the biosynthesis of tetrapyrroles such as hemes and chlorophylls.29?31 Enzymes from other families catalyze modification of the aminoacyl moiety of aa-tRNAs (i.e., while this moiety is still attached to tRNAs) to generate aa-tRNAs loaded with asparagine, glutamine, formylmethionine, cysteine, or selenocysteine.15,32 The past decade has seen the identification of new aa-tRNA-dependent enzyme families, all of which are involved in the biosynthesis of microbial secondary metabolites,33?40 referred to hereafter asNPs (Figure 2).
A fascinating read...
Esoteric I know, but of interest certainly to chemists and biochemists.
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