Perspective The potential of glyoxylate as a prebiotic source molecule and a reactant in protometabolic pathways-The glyoxylose reaction

Recent work has demonstrated glyoxylate as a versatile source molecule and reactant under plausible prebiotic conditions, giving rise to protometabolic analogs of the r-TCA cycle while enabling the synthesis of hydroxy acids, a-amino acids, and orotate. These observations suggest that glyoxylate, as a "carboxylated-formaldehyde"equivalent, has the potential to play an even greater role in prebiotic chemistry, providing an alternative to formaldehyde-based reactions. Thus, and inspired by the Eschenmoser's glyoxylate scenario, we propose a distinct "glyoxylose reaction"framework where the initial formation of glycolaldehyde from glyoxylate is followed by a series of repetitive (1) aldol condensations with glyoxylate, (2) carbonyl migrations, and (3) decarboxylations. This alternative to the formose reaction is hypothesized to provide linear sugars and sugar acids while harboring the potential for autocatalytic pathways. A demonstration of this chemistry would expand the role of glyoxylate as a versatile molecule in prebiotic chemistry and stimulate further the search for its prebiotic provenance.