Game over? Nick Lane wants another round

Image: A scene from “Molecular Machines – ATP Synthase: The Power Plant of the Cell”, via Discovery Institute.

The score is 36-0, but Darwin’s team is not ready to take it. Lehigh University biochemist Michael Behe, writing for World Magazine (see our coverage here), described how he attended a conference of scientists to hear Nobel Prize winner John E. Walker, the world’s expert on ATP synthase, explain how it might have evolved. For design advocates, this rotary motor is a model of smart design. Walker, who shared a Nobel Prize for elucidating the rotary mechanism of the engine, spent all of his time describing the intricacies of this molecular machine and never offered an evolutionary explanation until the Q&A session. Then he was asked directly how an insane process could produce such stunning work. Walker stumbled, offering only a shred of speculation that he must have arisen “Slowly, through some sort of intermediary or other.” It was then that Behe, out of earshot, whispered two simple words, “Game over.”

Game over. The losing team heads for the showers with their heads down. Team Darwin’s MVP had just been retired in the bottom of the ninth. Calling the game in such an obvious wipeout would have been redundant. The crowd comes out of the stands. Suddenly, eight players are running on the field! “Wait! Wait!” they are crying. “Let’s have a batting time!”

The rescue team, led by Nick Lane of University College London, waves a paper above their heads. It’s just off the press PLOS Biology, titled “A Prebiotic Basis for ATP as a Universal Energy Currency”. Lane shouts, We have the middleman! It’s ACP! One of the referees looks at the paper for a minute. Will it be worth calling teams back to the field for another round?

A plausible scenario?

The gist of the hypothesis is that acetyl phosphate (AcP), a simple molecule with the formula C2H5O5P, can phosphorylate ADP to ATP in water, if the ferric ion (Fe3+) is present. The team believe their lab work offers a plausible scenario for the formation of prebiotic ATP without the need for ATP synthase.

ATP is universally conserved as the primary energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep preservation suggests that ATP appeared at an early stage of biochemical evolution. Still the synthesis of purines requires 6 phosphorylation steps linked to the hydrolysis of ATP.This autocatalytic requirement for ATP to synthesize ATP implies the need for a prebiotic ATP equivalentwhich could lead protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically by ATP rather than other nucleoside triphosphates, remains a mystery. Here we show that the deep conservation of ATP might reflect its prebiotic chemistry in relationship with another universally conserved intermediate, acetyl phosphate (AcP), which bridges thioester and phosphate metabolism by linking acetyl CoA to phosphorylation at the substrate of ADP. We confirm the previous results showing that AcP can phosphorylate ADP to ATP in nearly 20% yield in water in the presence of Fe3+ions. We then show that Fe3+ and AcP are surprisingly favored. [Emphasis added.]

It looks impressive. Can this work?

The team informs the referee of the surprising additional advantages of their intermediary. Visions of the Miller spark apparatus come to mind:

Surprisinglyour results show that maximum ATP synthesis occurred at high water activity and low ion concentrations, indicating that prebiotic ATP synthesis would be more feasible in freshwater systems.Likewise, ferrous iron can be oxidized to ferric iron by photochemical reactions or oxidants such as NO derived from volcanic emissions, meteorite impacts or lightning strikes, which also refers to terrestrial geothermal systems as a plausible environment for aqueous ATP synthesis.

questions and answers

What about hydrothermal vents?, asks the referee. Aren’t they the preferred places for prebiotic environments? “[O]Our results do not exclude submarine hydrothermal systems as potential environments for this chemistry,” they rejoice. But that could not happen today, they explain, because “high concentrations of Mg2+ (50 mM) and Ca2+ (10 mM) prevented ATP synthesis, implying that this chemistry would not be favored in modern oceans. The referee, frowning a little, senses a special pleading unfolding.

Other referees approach to see what it is. After listening, they start asking questions.

Have you tried this in a natural setting? No, we purchased chemicals from Fischer and Sigma-Aldrich and then mixed them in our lab under controlled conditions. (See Materials and Methods section.)

How did you go about linking the ingredients? We used store-bought catalysts and mixed them with store-bought nucleotides and phosphorylating agents. Then we shook them and heated them.

Why do you think this represents a plausible prebiotic environment? “AcP is unique among a panel of relevant phosphorylating agents in that it can phosphorylate ADP to ATP, in water, in the presence of Fe3+. AcP is readily formed by prebiotic chemistry and remains central to prokaryotic metabolism, making it the most plausible precursor to ATP as a biochemical phosphorylator.

Are you likely to find sufficient concentrations of AcP and ferric ions in natural water conditions for this to occur on early Earth? Uh, we haven’t tested that.

Wait a second; adenosine is a nucleoside base that includes ribose. How did it form in water? It’s a problem, we agree.

Have you tested chirality? Uh no.

Did you find a plausible container to hold the ATP? That wasn’t part of our investigation, no.

OK, so you get ATP under special conditions. ATP has a half-life of less than 5 minutes in water. Do you expect it to hang around long enough to be useful in a protocell? We haven’t thought about it in this article, no.

The ATP is obviously not alive. What would happen next? Presumably some primitive metabolic process could use it to produce energy.

Like what? “Recent experimental work shows that the core of autotrophic metabolism can occur spontaneously in the absence of genes and enzymes. This includes non-enzymatic equivalents of the acetyl-CoA pathway and parts of the reverse Krebs cycle, glycolysis and pentose phosphate pathway, gluconeogenesis, and amino acid biosynthesis. Recent work demonstrates that some nucleobases can also be formed following universally conserved biosynthetic pathways, using transition metal ions as catalysts. The idea that ATP might have arisen as a product of protometabolism from H2 and CO2 is therefore not unreasonable…”.

What exactly is “protometabolism”? Does it have meaning outside of a living context? (Silent gazes.)

Who decides what is reasonable? I suppose so.

The article states that “the biological synthesis of purines specifically involves 6 phosphorylation steps that are catalyzed by ATP in modern cells”. Adenine is a purine. How do you overcome the chicken and egg problem of needing ATP to make ATP?“If ATP did indeed form in a monomer via biomimetic protometabolism, then an earlier ATP equivalent must have driven the phosphorylation steps in purine synthesis.”

Can you describe a plausible earlier ATP equivalent? In fact, “a major question for prebiotic chemistry is how an energy money power might work” if not ATP.

And how did the ATP come to replace him, whoever he is? “Why this early phosphorylating agent was replaced, and specifically by ATP rather than other nucleoside triphosphates, remains a mystery.”

So how did your simple ATP generation process get replaced by ATP synthase? Well, it is well known that “ATP synthase fuels an imbalance in the ratio of ADP to ATP that is 10 orders of magnitude above the balance in the cytosol of modern cells. The drivers molecules such as ATP synthase use ratchet-like mechanical mechanisms to convert environmental redox imbalances into a highly skewed ratio of ADP to ATP, but we cannot say how this happened.

But how could a simple prebiotic system composed mostly of monomers sustain an imbalance in the ATP to ADP ratio that fuels labor? Well, “One possibility is that dynamic environments can maintain critical imbalances over short distances such as protocellular membranes.”

Didn’t you just assume the existence of a protocell with a membrane? Where did they come from? Listen, we’re not trying to paint a complete picture of the origin of life. We are simply trying to explain why ATP is the universal energy currency for life as it exists today, and how it came to emerge.

Emerged…by chance, you mean? Isn’t that circular reasoning? How? What other possibility is there?

There is intelligence, the only cause ever observed capable of assembling complex parts into a functional whole. Sorry; we thought it was a science baseball field.

He is. So what is your explanation of functional information in the simplest life? Your newspaper admits that “ATP links energy metabolism to genetic information. What is the source of this genetic information? Uh, some kind of middleman or whatever.

The referees gather and shout “GAME OVER!”

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