{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Woodard AM"],"funding":["Ministerio de Ciencia e Innovaci?n","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["14328-14340"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11225102"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["146(20)"],"pubmed_abstract":["The Gram-negative selective antibiotic darobactin A has attracted interest owing to its intriguing fused bicyclic structure and unique targeting of the outer membrane protein BamA. Darobactin, a ribosomally synthesized and post-translationally modified peptide (RiPP), is produced by a radical <i>S</i>-adenosyl methionine (rSAM)-dependent enzyme (DarE) and contains one ether and one C-C cross-link. Herein, we analyze the substrate tolerance of DarE and describe an underlying catalytic principle of the enzyme. These efforts produced 51 enzymatically modified darobactin variants, revealing that DarE can install the ether and C-C cross-links independently and in different locations on the substrate. Notable variants with fused bicyclic structures were characterized, including darobactin W3Y, w"],"journal":["Journal of the American Chemical Society"],"pubmed_title":["Darobactin Substrate Engineering and Computation Show Radical Stability Governs Ether versus C-C Bond Formation."],"pmcid":["PMC11225102"],"funding_grant_id":["CEX2021-001136-S","R01GM123998","R01 GM123998","IJC2020-045506-I","PID2021-125946OB-I00"],"pubmed_authors":["Mitchell DA","Peccati F","Navo CD","Woodard AM","Jimenez-Oses G"],"additional_accession":[]},"is_claimable":false,"name":"Darobactin Substrate Engineering and Computation Show Radical Stability Governs Ether versus C-C Bond Formation.","description":"The Gram-negative selective antibiotic darobactin A has attracted interest owing to its intriguing fused bicyclic structure and unique targeting of the outer membrane protein BamA. Darobactin, a ribosomally synthesized and post-translationally modified peptide (RiPP), is produced by a radical <i>S</i>-adenosyl methionine (rSAM)-dependent enzyme (DarE) and contains one ether and one C-C cross-link. Herein, we analyze the substrate tolerance of DarE and describe an underlying catalytic principle of the enzyme. These efforts produced 51 enzymatically modified darobactin variants, revealing that DarE can install the ether and C-C cross-links independently and in different locations on the substrate. Notable variants with fused bicyclic structures were characterized, including darobactin W3Y, w","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-04-30T21:28:54.964Z","creation":"2025-04-04T12:21:44.501Z"},"accession":"S-EPMC11225102","cross_references":{"pubmed":["38728535"],"doi":["10.1021/jacs.4c03994"]}}