Gober Joshua G, Brustad Eric M
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curr Opin Chem Biol. 2016 Dec;35:124-132. doi: 10.1016/j.cbpa.2016.09.004. Epub 2016 Sep 30.
Despite increasing interest in using enzymes as tools for synthesis, many reactions discovered through the creativity of synthetic chemists remain beyond the scope of biocatalysis. This vacancy in the field has compelled researchers to develop strategies to adapt protein scaffolds for new reactivity. Heme proteins have recently been shown to activate synthetic precursors to generate reactive metallocarbenoid and metallonitrenoid species that enable the biosynthetic construction of novel C-C, C-N, and other bonds using mechanisms not previously explored by Nature. By interrogating heme proteins with synthetic, non-natural reagents, scientists are merging the reaction space traditionally dominated by organocatalysis and transition metal catalysis with the mild reaction conditions, selectivity, and adaptability imparted by native protein scaffolds.
尽管人们对使用酶作为合成工具的兴趣日益浓厚，但许多通过合成化学家的创造力发现的反应仍超出了生物催化的范围。该领域的这一空白促使研究人员开发策略，以使蛋白质支架适应新的反应性。最近研究表明，血红素蛋白可激活合成前体，生成反应性金属卡宾和金属氮宾物种，从而利用自然界以前未探索过的机制进行新型碳-碳、碳-氮及其他键的生物合成构建。通过用合成的非天然试剂研究血红素蛋白，科学家们正在将传统上由有机催化和过渡金属催化主导的反应空间与天然蛋白质支架赋予的温和反应条件、选择性和适应性相结合。
