Early metabolism without phosphate

This week a very interesting new paper was published that explores the nature of ancient (perhaps prebiotic) chemistry that could have undergirded the kind of metabolism that we now associate with life.

If you have ever taken a biology class, then you have learned about ATP. (And perhaps then forgotten about. Understandable.) ATP is the energy currency of almost all life forms. Cells convert other kinds of energy to ATP, which is then a standard “power pack” that can be plugged into all sorts of other chemical reactions in the cell. The P in ATP is phosphate. It’s hard to picture life without phosphate and ATP. But there must have been some kind of biochemistry before phosphate, because ATP is made by fairly elaborate metabolic systems. When thinking about biochemistry in the early days of life (or before life), it seems we need metabolism that can be powered without relying on chemical conversion of energy into currency.

In the new paper, the scientists used a systems biology approach to look at all metabolism on earth after all phosphate-dependent components are erased from the picture. They find what appears to be a “core” phosphate-free metabolic system that can run without the need for ATP.

The paper is pretty technical, and the accompanying mini-review is too, but the story is worth a look. And the paper is open access. I don’t think the mini-review is open access but I will be happy to send it to anyone who can’t get it online. The paper also includes a “PaperClip” which is a nice audio conversation with the authors.

It’s not my main area of expertise but I would be glad to answer questions.

Paper: Remnants of an Ancient Metabolism without Phosphate
Mini-reivew: Energy in Ancient Metabolism


Thanks for spotting this paper. I, too, am not an expert in this field, but ever since attending lectures by Crick and Edelman describing early work in this area, I have been fascinated by this “Gap of all Gaps” that science is trying to fill. it’s not a repeatable experiment that scientists prefer, but I’m sure that a feasible scenario will be forthcoming soon. I can believe our Creator approves of, and is amused by, mankind’s efforts to figure out 'how in Heaven did He manage it?'
Al Leo

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That is indeed a super interesting development! I got through the paper last night, and for the most part it made sense, though I wish I had googled ‘systems biology’ first because I was reading it with a little confusion over whether it was all based strictly on computer modeling, or if they were doing actual chemistry at any point in coming to their conclusions. My last impression (ten years ago) was that modeling protein folds and such wasn’t very reliable yet.

Is the thioester cycle something actually functioning in some/all cells? Or are there just pieces of it scattered all over the kingdoms of life?

I would love to read the mini-review as well, if possible!

There are many kinds of modeling, and the metabolism paper isn’t about folds.

Yes, thioesters are ubiquitous, and their breakthrough moment was just a few months ago in this paper:

Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions
Minireview in that issue of Nature: Chemistry: Small molecular replicators go organic

The most famous thioester in today’s metabolism is acetyl-CoA.

I sent the Cell minireview offline, glad to provide the link on request.

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