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Absorbing catalytic modes from organocatalysis may be fruitful for designing new\u2010to\u2010nature enzymes with novel functions. Herein we report a newly designed artificial enzyme harboring a catalytic pyrrolidine residue that catalyzes the asymmetric Michael addition of cyclic ketones to nitroolefins through enamine activation with high efficiency. Diverse chiral \u03b3\u2010nitro cyclic ketones with two stereocenters were efficiently prepared with excellent stereoselectivity (up to 97\u2009% e.e., &gt;20\u2009:\u20091 d.r.) and good yield (up to 86\u2009%). This work provides an efficient biocatalytic strategy for cyclic ketone functionalization, and highlights the usefulness of artificial enzymes for extending biocatalysis to further non\u2010natural reactions.<\/jats:p>","DOI":"10.1002\/anie.202404312","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T01:09:48Z","timestamp":1716512988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis"],"prefix":"10.1002","volume":"63","author":[{"given":"Zhixi","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Life Sciences and Health Engineering Jiangnan University  Wuxi 214122 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinru","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Health 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