{"id":119379,"date":"2021-02-10T00:22:44","date_gmt":"2021-02-10T08:22:44","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2021\/02\/efficient-lewis-acid-catalysis-of-an-abiological-reaction-in-a-de-novo-protein-scaffold"},"modified":"2021-02-10T00:22:44","modified_gmt":"2021-02-10T08:22:44","slug":"efficient-lewis-acid-catalysis-of-an-abiological-reaction-in-a-de-novo-protein-scaffold","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2021\/02\/efficient-lewis-acid-catalysis-of-an-abiological-reaction-in-a-de-novo-protein-scaffold","title":{"rendered":"Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/efficient-lewis-acid-catalysis-of-an-abiological-reaction-in-a-de-novo-protein-scaffold.jpg\"><\/a><\/p>\n<p>New enzyme catalysts are usually engineered by repurposing the active sites of natural proteins. Here we show that design and directed evolution can be used to transform a non-natural, functionally naive zinc-binding protein into a highly active catalyst for an abiological hetero-Diels\u2013Alder reaction. The artificial metalloenzyme achieves 10<sup>4<\/sup> turnovers per active site, exerts absolute control over reaction pathway and product stereochemistry, and displays a catalytic proficiency (1\/<i>K<\/i><sub>TS<\/sub> = 2.9 \u00d7 10<sup>10<\/sup> M<sup>\u22121<\/sup>) that exceeds all previously characterized Diels\u2013Alderases. These properties capitalize on effective Lewis acid catalysis, a chemical strategy for accelerating Diels\u2013Alder reactions common in the laboratory but so far unknown in nature. Extension of this approach to other metal ions and other de novo scaffolds may propel the design field in exciting new directions.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>New enzyme catalysts are usually engineered by repurposing the active sites of natural proteins. Here we show that design and directed evolution can be used to transform a non-natural, functionally naive zinc-binding protein into a highly active catalyst for an abiological hetero-Diels\u2013Alder reaction. The artificial metalloenzyme achieves 104 turnovers per active site, exerts absolute control [\u2026]<\/p>\n","protected":false},"author":427,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[19,385],"tags":[],"class_list":["post-119379","post","type-post","status-publish","format-standard","hentry","category-chemistry","category-evolution"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/119379","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/427"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=119379"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/119379\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=119379"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=119379"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=119379"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}