{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:04:01Z","timestamp":1790085841803,"version":"4.0.1"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"18","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100022928","name":"Shiv Nadar Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Unlike CYP450 (cysteine-ligated), the axial ligations in Catalase (tyrosine-ligated) and CYP411-BM3 (serine-ligated) are different, which is generally attributed to the different catalytic efficiencies of these enzymes. Studies show that an interplay between push\u2013pull effects due to different ligations modulates the reactivity of different enzymes. In the present study, we employ extensive MD simulation and a hybrid QM\/MM approach to demonstrate that differences in the axial ligation in conjunction with protein residues generate a preorganized local electric field (LEF) that, in turn, controls the reactivity of the different families of heme-containing enzymes. Considering an example of the epoxidation reaction in trans-\u03b2-methylstyrene, we show that, by strategically mutating catalase and CYP411-BM3 to design a preorganized LEF that matches the native LEF of CYP450 monooxygenase, we can evolve catalase and CYP411-BM3 with reactivity similar to that of CYP450. This study shows that by tuning the preorganized LEF of an enzyme through strategic mutations of charged and polar residues, a secondary, non-native function can be evolved.<\/jats:p>","DOI":"10.1021\/acs.jctc.6c01060","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:06:48Z","timestamp":1788451608000},"page":"9538-9547","source":"Crossref","is-referenced-by-count":0,"title":["Tweaking Enzymatic Electric Field Can Evolve CYP450-like\nActivity in Catalase and CYP-P411 Enzymes"],"prefix":"10.1021","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7453-5150","authenticated-orcid":true,"given":"Dinesh","family":"Singh","sequence":"first","affiliation":[{"name":"Shiv Nadar Institution of Eminence , , ,","place":["Delhi NCR, India, 201314"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8865-7602","authenticated-orcid":true,"given":"Kshatresh Dutta","family":"Dubey","sequence":"additional","affiliation":[{"name":"Shiv Nadar Institution of Eminence , , ,","place":["Delhi NCR, India, 201314"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"5","key":"2026092209080845100_cit1","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1021\/acs.chemrev.7b00373","article-title":"Oxygen activation and radical transformations in heme\nproteins and metalloporphyrins","volume":"118","author":"Huang","year":"2018","journal-title":"Chem. 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