美国斯克里普斯研究所Ramanarayanan Krishnamurthy团队的一项最新研究发现，从α-酮酸到α-氨基酸和乳清酸酯的前生物合成可能是向现代代谢途径过渡的重要一环。这一研究成果于2022年7月28日发表在国际顶尖学术期刊《自然-化学》上。

该研究表明，α-酮酸与氰化物和氨通过Bucherer-Bergs反应可生成相应的α-氨基酸。草酰乙酸通过N-氨基甲酰基天冬氨酸酯转化为天冬氨酸酯的高效前生物合成可以同时形成二氢乳清酸酯，而这与作为嘧啶碱基前体的乳清酸酯的生化合成是平行的。乙醛酸形成甘氨酸和乳清酸酯，并与丙二酸酯和尿素反应生成天冬氨酸酯和二氢乳清酸酯。这些结果与之前证明的类似Krebs循环的前生物合成体系一起表明，可能存在一个自然出现的所有生物合成途径的共同前驱体系，具有从前生物化学无缝过渡到现代代谢途径的潜力。

据悉，醛类的Strecker反应是解释α-氨基酸前生物起源的重要预设途径。然而，生物利用α-酮酸的转氨基作用来合成氨基酸，然后再转化为碱基，这意味着从生命起源前的合成途径（包括Strecker反应）到今天的生物合成途径中，发生了一种生物或非生物的进化转变。

附：英文原文

Title: Prebiotic synthesis of α-amino acids and orotate from α-ketoacids potentiates transition to extant metabolic pathways

Author: Pulletikurti, Sunil, Yadav, Mahipal, Springsteen, Greg, Krishnamurthy, Ramanarayanan

Issue&Volume: 2022-07-28

Abstract: The Strecker reaction of aldehydes is the pre-eminent pathway to explain the prebiotic origins of α-amino acids. However, biology employs transamination of α-ketoacids to synthesize amino acids which are then transformed to nucleobases, implying an evolutionary switch—abiotically or biotically—of a prebiotic pathway involving the Strecker reaction into today’s biosynthetic pathways. Here we show that α-ketoacids react with cyanide and ammonia sources to form the corresponding α-amino acids through the Bucherer–Bergs pathway. An efficient prebiotic transformation of oxaloacetate to aspartate via N-carbamoyl aspartate enables the simultaneous formation of dihydroorotate, paralleling the biochemical synthesis of orotate as the precursor to pyrimidine nucleobases. Glyoxylate forms both glycine and orotate and reacts with malonate and urea to form aspartate and dihydroorotate. These results, along with the previously demonstrated protometabolic analogues of the Krebs cycle, suggest that there can be a natural emergence of congruent forerunners of biological pathways with the potential for seamless transition from prebiotic chemistry to modern metabolism.

DOI: 10.1038/s41557-022-00999-w

Source: https://www.nature.com/articles/s41557-022-00999-w