Every living organism engages in metabolism, a process by which substances are absorbed, synthesized and degraded for various uses to sustain life. This process, encompassing all chemical changes that occur throughout the lifetime of organisms, requires energy generated through the phosphorylation reactions of sugars. Essential components that make life possible – for example, ribonucleic acid, (RNA), deoxyribonucleic acid (DNA) and adenosine triphosphate (ATP) – are the products of phosphorylation reactions, or the addition of phosphoryl groups to substances.

Though in vivo phosphorylation occurs spontaneously using ATP and reaction-specific enzymes, it is not a spontaneous reaction thermodynamically, known to occur only within cells. Explaining the mechanisms of intracellular phosphorylation, therefore, has been the first step to cracking the mystery of the origin of life.

Researchers at the IBS Center for Plant Aging Research (Director NAM Hong Gil) worked with a research team from Stanford University and discovered that ribose, glucose and other sugars are spontaneously phosphorylated at accelerated speeds inside micrometer-sized water drops. Their observation has shaken the conventional view – such reactions do not spontaneously occur in an aqueous solution under lab environments – and shed new light on investigating life phenomena by triggering a vital life process, phosphorylation, outside living organisms.

▲ Mass spectra of the sugar phosphates produced from microdroplet reactions.
(A) Schematic diagram showing synthesis of the sugar phosphates produced from the reaction
between sugars and phosphoric acid in microdroplets, recorded by a high-resolution MS.

T he occur rence of diver se metabolic reactions is confined to intracellular space inside of an organism. In order to capture a phosphorylation reaction occurring in physically cell-like environments, the researchers chose micrometer-sized droplets and observed that sugar phosphates are produced there within a few microseconds. Unlike in bulk solution, the entropy in the droplets does not decrease; the surface electrical field of the droplets alters the material orientation and reaction energy, which presumably made the reaction possible.

▲ Progression of the phosphorylation reaction between D-ribose and phosphoric acid
in charged and uncharged aqueous microdroplets. Time-course changes in the ion count ratio
between D-ribose-1-phosphate and unreacted D-ribose in (A) charged and (B) uncharged microdroplets.

The team’s discovery indicates that the first life may have sprung from a water drop containing small, simple molecules. Through previous research, the team already demonstrated that micrometer-sized aqueous droplets are favorable conditions for diverse chemical reactions, where their reactions rates are accelerated 1000 to 1 million-fold. As ribose 1-phosphate, one of the sugar phosphates produced in the water drops, is a basic building block of RNA’s nucleobases, the research has suggested a possibility of these microdroplets as a synthetic pathway for nucleobases and RNA.

These results are expected to deepen the understanding of metabolism and provide a reliable explanation on how life began and why it has to end.