Alfonzo Edwin, Das Anuvab, Arnold Frances H
Division of Chemistry and Chemical Engineering, 210-41, California Institute of Technology, 1200 East California Blvd, Pasadena, CA 91125, USA.
Curr Opin Green Sustain Chem. 2022 Dec;38. doi: 10.1016/j.cogsc.2022.100701. Epub 2022 Sep 15.
Noncanonical amino acids (ncAAs) merge the conformational behavior and native interactions of proteinogenic amino acids with nonnative chemical motifs and have proven invaluable in developing modern therapeutics. This blending of native and nonnative characteristics has resulted in essential drugs like nirmatrelvir, which comprises three ncAAs and is used to treat COVID-19. Enzymes are appearing prominently in recent syntheses of ncAAs, where they demonstrate impressive control over the stereocenters and functional groups found therein. Here we review recent efforts to expand the biocatalyst arsenal for synthesizing ncAAs with natural enzymes. We also discuss how new-to-nature enzymes can contribute to this effort by catalyzing reactions inspired by the vast repertoire of chemical catalysis and acting on substrates that would otherwise not be used in synthesizing ncAAs. Abiotic enzyme-catalyzed reactions exploit the selectivity afforded by a macromolecular catalyst to access molecules not available to natural enzymes and perhaps not even chemical catalysis.
非标准氨基酸(ncAAs)将蛋白质原性氨基酸的构象行为和天然相互作用与非天然化学基序相结合,在开发现代疗法方面已证明具有不可估量的价值。这种天然和非天然特征的融合产生了像奈玛特韦这样的重要药物,它包含三种非标准氨基酸,用于治疗新冠病毒。酶在最近非标准氨基酸的合成中显著出现,在这些合成中,它们对其中发现的立体中心和官能团表现出令人印象深刻的控制能力。在这里,我们回顾了最近利用天然酶扩大非标准氨基酸生物催化剂库的努力。我们还讨论了新型酶如何通过催化受大量化学催化反应启发的反应以及作用于否则不会用于合成非标准氨基酸的底物来为这一努力做出贡献。非生物酶催化反应利用大分子催化剂提供的选择性来获取天然酶无法获得甚至化学催化也无法获得的分子。