9xb2
trans-Aconitate Decarboxylase Tad1
Structural highlights
FunctionTAD1_MYCMD Trans-aconitate decarboxylase; part of the gene cluster that mediates the biosynthesis of itaconic acid and 2-hydroxyparaconate (PubMed:26639528, PubMed:27750034). Cis-aconitate is secreted by the mitochondrial tricarboxylate transporter MTT1. In the cytosol cis-aconitate is converted into trans-aconitate via isomerization by the aconitate-delta-isomerase ADI1 (PubMed:26639528). Decarboxylation of trans-aconitate by the trans-aconitate decarboxylase TAD1 then leads then to the production of itaconic acid (PubMed:26639528). The cytochrome P450 monooxygenase CYP3 further converts itaconate to 2-hydroxyparaconate via oxidation of the double bond, leading to a transient epoxide, which can subsequently be lactonized to produce 2-hydroxyparaconate (PubMed:27750034). Secretion of itaconate and possibly 2-hydroxyparaconate into the medium is mediated by the major facilitator ITP1 (PubMed:26639528, PubMed:27750034). The glyoxalase domain-containing protein RDO1 is not involved in the biosynthesis of itaconate and 2-hydroxyparaconate, however, it might play a role in the further conversion of 2-hydroxyparaconate to itatartarate (PubMed:27750034).[1] [2] SUMO_YEAST Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer (PubMed:9312010). Sumoylation, the attachment of SUMO to target proteins, regulates multiple cellular events (By similarity).[UniProtKB:O13351][3] Publication Abstract from PubMedTrans-aconitate decarboxylase (Tad1) catalyzes the conversion of trans-aconitate to itaconate, a compound of growing interest in biotechnology owing to its diverse applications as a platform chemical. Despite this potential, detailed biochemical and mechanistic insights into Tad1 remain incomplete. This study presents the heterologous expression, purification, and comprehensive biochemical characterization of Tad1 from Ustilago maydis. We determined its optimal pH and temperature, and cofactor requirements. Furthermore, we employed X-ray crystallography, molecular docking, and site-directed mutagenesis to elucidate key residues involved in substrate binding and catalysis, thereby establishing a molecular basis for its decarboxylase activity. Elucidating Tad1's catalytic mechanism and active site architecture is essential for overcoming current limitations in itaconate biosynthesis and advancing sustainable chemical production. Biochemical characterization and molecular mechanism study of trans-aconitate decarboxylase Tad1.,Lu Y, Zhang K, Wang C, Wu D, Huang X, Xu H, Ma H, Lu X Enzyme Microb Technol. 2026 Aug;199:110875. doi: 10.1016/j.enzmictec.2026.110875. , Epub 2026 Apr 22. PMID:42060999[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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