Beverly Fu, Hao Yang, Duncan J. Kountz, Maike N. Lundahl, Harry R. Beller, William E. Broderick, Joan B. Broderick, Brian H. Hoffman, Emily P. Balskus
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引用次数: 0
Abstract
Radical enzymes, including the evolutionarily ancient glycyl radical enzyme (GRE) family, catalyze chemically challenging reactions that are involved in a myriad of important biological processes. All GREs possess an essential, conserved backbone glycine that forms a stable catalytically essential α-carbon radical. Through close examination of the GRE family, we unexpectedly identified hundreds of noncanonical GRE homologues that encode either an alanine, serine, or threonine in place of the catalytic glycine residue. Contrary to a long-standing belief, we experimentally demonstrate that these aminoacyl radical enzymes (AAREs) form stable α-carbon radicals on the three cognate residues when activated by partner activating enzymes. The previously unrecognized AAREs are widespread in microbial genomes, highlighting their biological importance and potential for exhibiting new reactivity. Collectively, these studies expand the known radical chemistry of living systems while raising questions about the evolutionary emergence of the AAREs.
自由基酶,包括进化古老的甘氨酰自由基酶(GRE)家族,催化化学上具有挑战性的反应,参与了无数重要的生物过程。所有 GRE 都有一个重要的、保守的骨架甘氨酸,它能形成一个稳定的催化必需的 α 碳自由基。通过对 GRE 家族的仔细研究,我们意外地发现了数百个非规范的 GRE 同源物,它们用丙氨酸、丝氨酸或苏氨酸代替了催化的甘氨酸残基。与长期以来的观点相反,我们通过实验证明,这些氨基酰基酶(AAREs)在伙伴活化酶的激活下,会在三个同源残基上形成稳定的α-碳自由基。以前未被发现的 AAREs 广泛存在于微生物基因组中,突显了它们在生物学上的重要性和表现出新反应性的潜力。总之,这些研究扩展了已知的生命系统自由基化学,同时提出了关于 AAREs 进化出现的问题。
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