Department of Chemistry, University of York, Heslington York, YO10 5DD, UK.
GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
Angew Chem Int Ed Engl. 2023 Jan 26;62(5):e202214759. doi: 10.1002/anie.202214759. Epub 2022 Dec 22.
A lyophilized preparation of an unspecific peroxygenase variant from Agrocybe aegerita (rAaeUPO-PaDa-I-H) is a highly effective catalyst for the oxygenation of a diverse range of N-heterocyclic compounds. Scalable biocatalytic oxygenations (27 preparative examples, ca. 100 mg scale) have been developed across a wide range of substrates, including alkyl pyridines, bicyclic N-heterocycles and indoles. H O is the only stoichiometric oxidant needed, without auxiliary electron transport proteins, which is key to the practicality of the method. Reaction outcomes can be altered depending on whether hydrogen peroxide was delivered by syringe pump or through in situ generation using an alcohol oxidase from Pichia pastoris (PpAOX) and methanol as a co-substrate. Good synthetic yields (up to 84 %), regioselectivity and enantioselectivity (up to 99 % ee) were observed in some cases, highlighting the promise of UPOs as practical, versatile and scalable oxygenation biocatalysts.
一种来自糙皮侧耳（Agrocybe aegerita）的非特异性过氧化物酶变体的冻干制剂（rAaeUPO-PaDa-I-H）是一种高效的催化剂，可用于多种 N-杂环化合物的氧化。已经针对各种底物（包括烷基吡啶、双环 N-杂环和吲哚）开发了可扩展的生物催化氧化（27 个制备实例，约 100mg 规模）。该方法的关键是仅需 H 2 O 2 作为化学计量氧化剂，而无需辅助电子传递蛋白，这使其具有实际应用的潜力。根据是否通过注射器泵或使用巴斯德毕赤酵母醇氧化酶（PpAOX）和甲醇作为共底物原位生成来输送过氧化氢，可以改变反应结果。在某些情况下，观察到了良好的合成收率（高达 84%）、区域选择性和对映选择性（高达 99%ee），这突显了 UPO 作为实用、多功能和可扩展的氧化生物催化剂的前景。
