Lichman Benjamin R, O'Connor Sarah E, Kries Hajo
Department of Biological Chemistry, The John Innes Centre, Colney Lane, Norwich, UK.
Current address: Department of Biology, University of York, York, YO10 5YW, UK.
Chemistry. 2019 May 17;25(28):6864-6877. doi: 10.1002/chem.201805412. Epub 2019 Mar 12.
Long sought after [4+2] cyclases have sprouted up in numerous biosynthetic pathways in recent years, raising hopes for biocatalytic solutions to cycloaddition catalysis, an important problem in chemical synthesis. In a few cases, detailed pictures of the inner workings of these catalysts have emerged, but intense efforts to gain deeper understanding are underway by means of crystallography and computational modelling. This Minireview aims to shed light on the catalytic strategies that this highly diverse family of enzymes employs to accelerate and direct the course of [4+2] cycloadditions with reference to small-molecule catalysts and designer enzymes. These catalytic strategies include oxidative or reductive triggers and lid-like movements of enzyme domains. A precise understanding of natural cycloaddition catalysts will be instrumental for customizing them for various synthetic applications.
长期以来备受追寻的[4+2]环化酶近年来已在众多生物合成途径中涌现，这为化学合成中的一个重要问题——环加成催化的生物催化解决方案带来了希望。在少数情况下，这些催化剂内部运作的详细情况已浮出水面，但人们正通过晶体学和计算建模等手段，为更深入地理解它们而进行着大量努力。本微型综述旨在参照小分子催化剂和设计酶，阐明这一高度多样化的酶家族用于加速和引导[4+2]环加成反应进程的催化策略。这些催化策略包括氧化或还原触发以及酶结构域类似盖子的运动。精确了解天然环加成催化剂将有助于对其进行定制以用于各种合成应用。
