{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11"],"submitter":["Teng YB"],"pubmed_abstract":["Pictet-Spengler (PS) reactions are pivotal in the biosynthesis of bioactive alkaloids and pharmaceuticals, yet key structural details underlying their enzymatic catalysis remain insufficiently understood. We identified AsKslB from <i>Actinosynnema</i> sp. ALI-1.44 as a Pictet-Spenglerase with broad substrate scope that catalyzes the stereoselective condensation of l-tryptophan (l-Trp) and α-ketoglutarate (α-KG) to form kitasetalic acid (KA), a tetrahydro-β-carboline (THβC). High-resolution crystal structures of apo, substrate-, intermediate-, and product-bound forms elucidate the full catalytic trajectory and key residues. Crucially, the elusive iminium ion intermediate (IM-1) and a synchronously released water molecule are captured, providing direct structural evidence for the initiating cyclization step of Pictet-Spengler reaction. Glu276 undergoes conformational changes essential for catalysis. These findings offer detailed mechanistic insights into Pictet-Spenglerase function and establish AsKslB as a promising biocatalyst for stereoselective <i>N</i>-heterocycle synthesis."],"journal":["Synthetic and systems biotechnology"],"pagination":["247-255"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12547825"],"repository":["biostudies-literature"],"pubmed_title":["Structural and functional insights into the iminium ion intermediate in AsKslB-mediated Pictet-Spengler reaction."],"pmcid":["PMC12547825"],"pubmed_authors":["Yang X","Liu X","Zou Z","Chen Q","Xie Y","Zhang X","Teng YB","Qiao Z","Xie C"],"additional_accession":[]},"is_claimable":false,"name":"Structural and functional insights into the iminium ion intermediate in AsKslB-mediated Pictet-Spengler reaction.","description":"Pictet-Spengler (PS) reactions are pivotal in the biosynthesis of bioactive alkaloids and pharmaceuticals, yet key structural details underlying their enzymatic catalysis remain insufficiently understood. We identified AsKslB from <i>Actinosynnema</i> sp. ALI-1.44 as a Pictet-Spenglerase with broad substrate scope that catalyzes the stereoselective condensation of l-tryptophan (l-Trp) and α-ketoglutarate (α-KG) to form kitasetalic acid (KA), a tetrahydro-β-carboline (THβC). High-resolution crystal structures of apo, substrate-, intermediate-, and product-bound forms elucidate the full catalytic trajectory and key residues. Crucially, the elusive iminium ion intermediate (IM-1) and a synchronously released water molecule are captured, providing direct structural evidence for the initiating cyclization step of Pictet-Spengler reaction. Glu276 undergoes conformational changes essential for catalysis. These findings offer detailed mechanistic insights into Pictet-Spenglerase function and establish AsKslB as a promising biocatalyst for stereoselective <i>N</i>-heterocycle synthesis.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Mar","modification":"2026-06-05T05:39:31.29Z","creation":"2026-06-03T03:07:45.74Z"},"accession":"S-EPMC12547825","cross_references":{"pubmed":["41141485"],"doi":["10.1016/j.synbio.2025.09.017"]}}