{"id":353,"date":"2023-12-29T18:41:09","date_gmt":"2023-12-29T18:41:09","guid":{"rendered":"https:\/\/pharmsci.createuky.net\/eromedaniel\/?p=353"},"modified":"2023-12-29T18:41:09","modified_gmt":"2023-12-29T18:41:09","slug":"engineering-radical-acyl-transferases-from-benzaldehyde-lyase","status":"publish","type":"post","link":"https:\/\/pharmsci.createuky.net\/eromedaniel\/article-reviews\/engineering-radical-acyl-transferases-from-benzaldehyde-lyase\/","title":{"rendered":"Engineering radical acyl transferases from benzaldehyde lyase"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Looking for a paper that combines your passion for enzyme engineering and photoredox catalysis? Look no further! In this paper, the authors report a &#8220;dual-catalyst system&#8221; that combines the organophotoredox catalyst eosin Y with a ThDP (thiamine diphosphate) enzyme that they engineered to function as a radical acyl transferase. Key take aways:<br><br>1. Two mutations, A480L and T481L, were made in ThDP-dependent enzyme benzaldehyde lyase (BAL) to introduce radical acyl transferase (RAT) capabilities. Using eosin Y as a photoredox catalyst, the authors show that 4-methoxybenzaldehyde and an aromatic N-(acyloxy)phthalamide can be fused by the engineered RAT to synthesize alpha-chiral ketones!<br><br>2. Different aromatic aldehydes and phthalimide derivatives were tested to survey the substrate scope. The authors demonstrate that with a few exceptions the high yield and enantioselectivity observed for the control reaction are retained! Seriously, the numbers are just beautiful.<br><br>3. To elucidate the mechanism of their engineered enzyme, the authors performed EPR spectroscopy and quenching (TEMPO) experiments alongside computational studies. Their investigations revealed that following green light-mediated oxidation of eosin Y, the Breslow intermediate (common to all ThDP-dependent enzymes as well as synthetic N-heterocylic carbene catalysts) undergoes a single electron transfer that converts it into a ketyl. N-(acyloxy)phthalamide radicals are also generated through interaction with an eosin Y radical anion in a subsequent step.<br><br>4. Based on their findings (listed above) the authors conclude that an enantioselective radical-radical cross coupling reaction between the ketyl and prochiral N-(acyloxy)phthalamide radicals leads to the formation of alpha-chiral ketones.<br><br>Limitations: Yields and enantiopurity do dwindle for some reactions, but are still decent. The authors also report that the reaction must be done in an inert atmosphere (N2) and requires green light.<br><br><a href=\"https:\/\/www.nature.com\/articles\/s41586-023-06822-x\" data-type=\"link\" data-id=\"https:\/\/www.nature.com\/articles\/s41586-023-06822-x\">Read the article here! <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Looking for a paper that combines your passion for enzyme engineering and photoredox catalysis? Look no further! In this paper, the authors report a &#8220;dual-catalyst system&#8221; that combines the organophotoredox catalyst eosin Y with a ThDP (thiamine diphosphate) enzyme that they engineered to function as a radical acyl transferase. Key take aways: 1. Two mutations, &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/pharmsci.createuky.net\/eromedaniel\/article-reviews\/engineering-radical-acyl-transferases-from-benzaldehyde-lyase\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Engineering radical acyl transferases from benzaldehyde lyase&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6],"tags":[],"class_list":["post-353","post","type-post","status-publish","format-standard","hentry","category-article-reviews"],"_links":{"self":[{"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/posts\/353","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/comments?post=353"}],"version-history":[{"count":1,"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/posts\/353\/revisions"}],"predecessor-version":[{"id":354,"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/posts\/353\/revisions\/354"}],"wp:attachment":[{"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/media?parent=353"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/categories?post=353"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/pharmsci.createuky.net\/eromedaniel\/wp-json\/wp\/v2\/tags?post=353"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}