I wish I had a nickel every time I hear that the “metabolome” — the collection of all of the small molecules which exist as intermediaries in the biochemical machinery of living cells — consists of only a few hundred metabolites. “The number of known metabolites present in many organisms (e.g., yeast) is 10- to 100-fold fewer than the number of genes or proteins,” said one paper, which later went on to say that the yeast metabolome was around 600 metabolites. Another says that the erstwhile laboratory favorite, the bacterium Escherichia coli, has “694 metabolites present in the in silico metabolome.”
The key words are “known” and “in silico”. Of course if you limit yourself to what you know about, or limit yourself to “in silico” databases of metabolites that other people know about, you won’t find anything new. But that doesn’t mean that we know what all of the metabolites are!
Leah C. Blasiak and Jon Clardy provide an excellent counterexample to the idea that we have a handle on the chemical diversity of microbes in a recent paper in the Journal of the American Chemical Society, which details their discovery of 3-formyltyrosine and related metabolites in a marine bacterium. Drs. Blasiak and Clardy went searching through genomic databases for genes that seemed to encode proteins similar to a newly discovered class of rather funky enzymes, the “ATP-grasp-type ligases”. They found an interesting set of genes from Pseudoalteromonas tunicata, a seabound bacterium which is often found on the surface of seaweed, floating debris, and intervetebrates. They moved those genes to E. coli cells, and then looked in cellular extracts for blips in their mass spectra that did not show up in E. coli cells. They found a few, and after extensive chemical characterization of those blips, they were ready to announce to the world that 3-formyltyrosine was a biologically produced metabolite.
It wasn’t in anyone’s database and hasn’t yet appeared in an in silico metabolome yet, to my knowledge, despite it having been in the Pseudoalteromonas tunicata metabolome for hundreds (at least) of years. How many more metabolites like 3-formyltyrosine are there waiting to be discovered? My money says, “more than a lot of people think.”