{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhao LP"],"funding":["National Science Foundation (NSF)","U.S. Department of Health & Human Services | National Institutes of Health (NIH)","U.S. Department of Health &amp; Human Services | National Institutes of Health","NIGMS NIH HHS","National Science Foundation"],"pagination":["1773-1782"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12854064"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(11)"],"pubmed_abstract":["Nonheme Fe enzymes are biologically important enzymes that use iron at their active site without incorporating a heme cofactor. Nonetheless, these enzymes remain largely underexploited in the development of new-to-nature biocatalytic reactions with synthetic utility. Here we report the repurposing and directed evolution of plant-derived nonheme Fe enzyme 1-aminocyclopropane-1-carboxylic acid oxidase into a nitrogen migratase to enable the efficient and enantioselective 1,3-nitrogen migration reaction on both secondary C(sp<sup>3</sup>)-H and tertiary C(sp<sup>3</sup>)-H bonds from racemic substrates. This results in enantioenriched α-trisubstituted as well as α-tetrasubstituted noncanonical amino acids with broad utility. Combined experimental and computational studies reveal an unusual stereoablative hydrogen atom transfer followed by a stereoselective C-N bond-forming radical rebound mechanism, which accounts for the excellent enantiocontrol observed in biocatalytic amino acid synthesis. The multiple open coordination sites of nonheme Fe enable simultaneous binding of reaction partners, offering opportunities for biocatalysis beyond heme enzymes."],"journal":["Nature chemical biology"],"pubmed_title":["Nonheme Fe 1,3-nitrogen migratases for asymmetric noncanonical amino acid synthesis."],"pmcid":["PMC12854064"],"funding_grant_id":["R35 GM147387","CHE-2400087","R35GM147387"],"pubmed_authors":["Liu H","Yang Y","Zhang Y","Mai BK","Liu P","Cheng L","Zhao LP"],"additional_accession":[]},"is_claimable":false,"name":"Nonheme Fe 1,3-nitrogen migratases for asymmetric noncanonical amino acid synthesis.","description":"Nonheme Fe enzymes are biologically important enzymes that use iron at their active site without incorporating a heme cofactor. Nonetheless, these enzymes remain largely underexploited in the development of new-to-nature biocatalytic reactions with synthetic utility. Here we report the repurposing and directed evolution of plant-derived nonheme Fe enzyme 1-aminocyclopropane-1-carboxylic acid oxidase into a nitrogen migratase to enable the efficient and enantioselective 1,3-nitrogen migration reaction on both secondary C(sp<sup>3</sup>)-H and tertiary C(sp<sup>3</sup>)-H bonds from racemic substrates. This results in enantioenriched α-trisubstituted as well as α-tetrasubstituted noncanonical amino acids with broad utility. Combined experimental and computational studies reveal an unusual stereoablative hydrogen atom transfer followed by a stereoselective C-N bond-forming radical rebound mechanism, which accounts for the excellent enantiocontrol observed in biocatalytic amino acid synthesis. The multiple open coordination sites of nonheme Fe enable simultaneous binding of reaction partners, offering opportunities for biocatalysis beyond heme enzymes.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-25T03:18:03.789Z","creation":"2026-06-25T03:08:07.614Z"},"accession":"S-EPMC12854064","cross_references":{"pubmed":["40629132"],"doi":["10.1038/s41589-025-01953-w"]}}