{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Guo N"],"funding":["United States NSF","MOST | National Key Research and Development Program of China (NKPs)","CAS | ICCAS | Beijing National Laboratory for Molecular Sciences (BNLMS)","National Natural Science Foundation of China","| National Natural Science Foundation of China"],"pagination":["e2504346122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12403149"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(34)"],"pubmed_abstract":["Berberine bridge enzyme (BBE)-like enzymes catalyze various oxidative cyclization and dehydrogenation reactions in natural product biosynthesis, but the molecular mechanism underlying the selectivity remains unknown. Here, we elucidated the catalytic mechanism of BBE-like oxidases from <i>Morus alba</i> involved in the oxidative cyclization and dehydrogenation of moracin C. X-ray crystal structures of a functionally promiscuous flavin adenine dinucleotide (FAD)-bound oxidase, MaDS1, with and without an oxidative dehydrogenation product were determined at 2.03 Å and 2.21 Å resolution, respectively. Structure-guided mutagenesis and sequence analysis have identified a conserved aspartic acid that directs the reaction toward the oxidative dehydrogenation pathway. A combination of density funct"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Aspartic acid residues in BBE-like enzymes from &lt;i&gt;Morus alba&lt;/i&gt; promote a function shift from oxidative cyclization to dehydrogenation."],"pmcid":["PMC12403149"],"funding_grant_id":["22322701","2022YFC3401500","BNLMS-CXX-202106","22193073","CHE-2153972","92253305"],"pubmed_authors":["Yang J","Zhou Q","Houk KN","Ding Q","Wu D","Guo N","Wang Q","Dong H","Fan J","Lei X","Gao L","Gu J","Liu F"],"additional_accession":[]},"is_claimable":false,"name":"Aspartic acid residues in BBE-like enzymes from &lt;i&gt;Morus alba&lt;/i&gt; promote a function shift from oxidative cyclization to dehydrogenation.","description":"Berberine bridge enzyme (BBE)-like enzymes catalyze various oxidative cyclization and dehydrogenation reactions in natural product biosynthesis, but the molecular mechanism underlying the selectivity remains unknown. Here, we elucidated the catalytic mechanism of BBE-like oxidases from <i>Morus alba</i> involved in the oxidative cyclization and dehydrogenation of moracin C. X-ray crystal structures of a functionally promiscuous flavin adenine dinucleotide (FAD)-bound oxidase, MaDS1, with and without an oxidative dehydrogenation product were determined at 2.03 Å and 2.21 Å resolution, respectively. Structure-guided mutagenesis and sequence analysis have identified a conserved aspartic acid that directs the reaction toward the oxidative dehydrogenation pathway. A combination of density funct","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-07-16T05:35:33.222Z","creation":"2026-07-09T10:39:15.958Z"},"accession":"S-EPMC12403149","cross_references":{"pubmed":["40828030"],"doi":["10.1073/pnas.2504346122"]}}