{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:02:37Z","timestamp":1791378157006,"version":"4.3.2"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Preparative biocatalytic synthesis of substituted pyrroles remains challenging despite recent advances in enzymatic \u03b1\u2010aminoketone generation. In this study, we report a concurrent chemoenzymatic cascade to disubstituted pyrroles based on threonine dehydrogenase (ThrDH)\u2010catalyzed generation of aminoacetone from\n                    <jats:sc>l<\/jats:sc>\n                    \u2010threonine that is intercepted in situ by Knorr pyrrole condensation with\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010dicarbonyl compounds. To overcome cofactor limitations at high substrate concentrations,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ThrDH was coupled to an alcohol dehydrogenase from\n                    <jats:italic>Rhodococcus ruber<\/jats:italic>\n                    DSM 44541 (ADH\u2010A), enabling dual\u2010function of the\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010dicarbonyl cosubstrate as both a hydride acceptor and pyrrole building\u2010block. The whole\u2010cell catalyst tolerated up to 8% (v\/v)\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010dicarbonyl and afforded pyrrole products in up to 90% yield and space\u2010time yields of 4.5\u00a0g L\n                    <jats:sup>\u22121<\/jats:sup>\n                    h\n                    <jats:sup>\u22121<\/jats:sup>\n                    . Preparative synthesis on a 100\u00a0mL scale furnished 4.3\u00a0g of pyrrole (279\u00a0mM, 93% isolated yield). Among the products obtained, the cascade provides direct access to a reported sunitinib intermediate, illustrating its potential utility for pharmaceutical synthesis. This work establishes ThrDHs as outstanding biocatalysts for heterocycle synthesis and demonstrates that amino acid feedstocks can be efficiently converted into substituted pyrroles through a scalable chemoenzymatic cascade.\n                  <\/jats:p>","DOI":"10.1002\/anie.6159381","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:39:53Z","timestamp":1790840393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual\u2010Function Cosubstrates Enable Threonine Dehydrogenase\u2010Driven Chemoenzymatic Pyrrole Synthesis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7464-240X","authenticated-orcid":false,"given":"Valentina","family":"Jurka\u0161","sequence":"first","affiliation":[{"name":"Austrian Centre of Industrial Biotechnology (ACIB)  Graz Austria"},{"name":"Institute of Molecular Biotechnology Graz University of Technology  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3618-824X","authenticated-orcid":false,"given":"Fabian M.","family":"Kulier","sequence":"additional","affiliation":[{"name":"Austrian Centre of Industrial Biotechnology (ACIB)  Graz Austria"},{"name":"Institute of Molecular Biotechnology Graz University of Technology  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3733-3824","authenticated-orcid":false,"given":"Jorge","family":"Gonz\u00e1lez\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Austrian Centre of Industrial Biotechnology (ACIB)  Graz Austria"},{"name":"Institute of Applied Synthetic Chemistry TU Wien Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5280-135X","authenticated-orcid":false,"given":"Carlotta","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Politecnico di Milano, Dipartimento Di Chimica Materiali ed Ingegneria Chimica \u201cGiulio Natta\u201d  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-9014","authenticated-orcid":false,"given":"Peter","family":"Both","sequence":"additional","affiliation":[{"name":"Axxence Slovakia s.r.o.  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