Cofactor (biochemistry) Both coenzymes (organic) and metal ions.
The RNA world had developed an elaborate biochemistry by the time that it developed proteins, meaning that a lot of evolution had taken place in it before then. Numerous coenzymes can be traced back to it with varying degrees of confidence, and a common feature of many of them is that many of them are
Heterocyclic compound - having rings with more than one element of atom in them. Nucleobases have carbon-nitrogen rings, and ribose, like other sugars, has a carbon-oxygen ring, and many coenzymes are like nucleobases in having carbon-nitrogen rings.
Cofactors are Remnants of Life’s Origin and Early Evolution - PMC
The RNA World is one of the most widely accepted hypotheses explaining the origin of the genetic system used by all organisms today. It proposes that the tripartite system of DNA, RNA, and proteins was preceded by one consisting solely of RNA, which both stored genetic information and performed the molecular functions encoded by that genetic information. Current research into a potential RNA World revolves around the catalytic properties of RNA-based enzymes, or ribozymes. Well before the discovery of ribozymes, Harold White proposed that evidence for a precursor RNA world could be found within modern proteins in the form of coenzymes, the majority of which contain nucleobases or nucleoside moieties, such as Coenzyme A and S-adenosyl methionine, or are themselves nucleotides, such as ATP and NADH (a dinucleotide). These coenzymes, White suggested, had been the catalytic active sites of ancient ribozymes, which transitioned to their current forms after the surrounding ribozyme scaffolds had been replaced by protein apoenzymes during the evolution of translation. Since its proposal four decades ago, this groundbreaking hypothesis has garnered support from several different research disciplines and motivated similar hypotheses about other classes of cofactors, most notably iron-sulfur cluster cofactors as remnants of the geochemical setting of the origin of life. Evidence from prebiotic geochemistry, ribozyme biochemistry, and evolutionary biology, increasingly supports these hypotheses. Certain coenzymes and cofactors may bridge modern biology with the past and can thus provide insights into the elusive and poorly-recorded period of the origin and early evolution of life.
I'll try to summarize. Much of RNA-world research has been on the catalytic ability of RNA. But another important piece of evidence is in coenzymes, organic cofactors of enzymes. Many of them are RNA-like, pointing to a RNA-world ancestry. But other kinds of cofactors are now also proposed for the RNA world, like iron-sulfur clusters.
Noting
Coenzymes as fossils of an earlier metabolic state - PubMed
with PDF version
Coenzymes as fossils of an earlier metabolic state - cofactors_molecular_fossils.pdf
Coenzymes are complex organic molecules which are essential for many enzyme-catalyzed reactions. At least 52% of the nearly 1750 enzymes recently catalogued (IUPAC-IUB, 1972) require a coenzyme for activity. Although there have been discussions of the evolution of coenzymes (Handler, 1963; Eakin, 1963), none have explained the curious fact that many coenzymes are nucleotides (NAD, NADP, FAD, coenzyme A, ATP, etc.) or contain cyclic nitrogenous bases which could be derived from nucleotides (thiamin pyrophosphate, tetrahydrofolate, pyridoxal phosphate, etc.) (Dixon & Webb, 1955) .
Then noting
The degree to which contemporary coenzymes reflect the proposed nucleic acid ancestry varies considerably. At one extreme are the tRNAs which Brewin (1972) has considered as polynucleotide enzymes, They also can be viewed as very large coenzymes which participate in the group transfer of amino acids. Another group of coenzymes are the mono and dinucleotide coenzymes whose structure contains catalytically inactive portions which presumably are retained for binding to proteins. The most cryptic group of coenzymes are those which are no longer nucleotides but rather are modified cyclic nitrogenous bases which could be derived from nucleotides. One such example is the hypothetical thiamin nucleotide shown in Fig.1.
There are coenzymes such as biotin and lipoic acid which do not bear any resemblance to nucleotides or nucleotide bases.
Many of them transfer something.
- Thiamine (B1) - RNA world (?) - 2-carbon groups, does "alpha-cleavage" (breaking a C-C bond near some part)
- Riboflavin (B2) - RINA world - Electrons
- Niacin (B3) - RNA world - Electrons
- Pantothenic acid (B5) - RNA world - Acetyl, other acyl groups (attachment at carboxyl groups)
- Pyridoxine (B6) - RNA world (?) - Amino, carboxyl groups
- Folic acid (B9) - RNA world (?) - Methyl, related groups
- Cobalamin (B12) - RNA world - Hydrogen, alkyl groups (alkanes: saturated hydrocarbons)
- S-adenosylmethionine (SAM) - RNA world - Methyl group
- ATP - RNA world - Phosphate group
- Biotin (B7) - (?) - CO2
- Lipoic acid - (?)
The protein-forming amino acid histidine has a nucleobase-like side chain, and it is the only one synthesized from a nucleotide. It is often found in the active sites of enzymes, where it does acid-base chemistry.
The palimpsest paper notes additional evidence: biosynthesis of porphyrins and terpenes. The authors of that paper then propose that both of them were in the RNA world.
Porphyrins and related compounds are rings of carbon-nitrogen rings, and they have two biosynthesis pathways. They converge at delta-aminolevulinic acid (or 5-), which goes the rest of the way.
- C5, Beale: glutamyl transfer RNA - Archaea, Bacteria except for alpha-proteobacteria, photosynthetic Eukarya
- C4, Shemin: glycine, succinyl coenzyme A - Alpha-proteobacteria, non-photosynthetic Eukarya
So the C5 pathway was the original one, and C4 was invented by some alpha-proteobacterium and then transmitted to eukaryotes when one of its descendants became a mitochondrion. C5 got back into eukaryotes when a cyanobacterium became a plastid / chloroplast.
Terpenes were likely the first membrane lipid, with fatty acids coming later.
That remnant paper mentioned prebiotic synthesis of porphyrins and some nucleobases, and possible prebiotic synthesis of pyridoxal (pyridoxine). It also mentioned some inorganic cofactors that are in early proteins and likely in the RNA world:
Fe-S clusters, Zn, Mo
Wikipedia's cofactor article mentions at least some organisms using these metal ions:
Mg, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, Cd, W
