{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:49:54Z","timestamp":1792043394637,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:p>\n                    The scale\u2010up of biocatalytic processes for pharmaceutical manufacture still presents key challenges. Here, we describe the development of a transaminase used in the manufacturing\u2010scale synthesis of niraparib, a small molecule poly(ADP\u2010ribose) polymerase (PARP) inhibitor. Realization of a commercial process began with the engineering of an improved enzyme variant over nine rounds of directed evolution. In tandem, process development was carried out, intensifying the substrate concentration and applying key insights on transaminase performance. The optimized process and enzyme were demonstrated over multiple batches at plant scale, and analysis of the CO\n                    <jats:sub>2<\/jats:sub>\n                    footprint per kilogram showed that the optimized process using the evolved enzyme had an 80% reduction in emission impact compared to pre\u2010evolution, highlighting the valuable improvements made through this multidisciplinary effort.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70508","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:35:00Z","timestamp":1790537700000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Realization of a Manufacturing\u2010Scale Synthesis of Niraparib Using an Evolved Transaminase"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0066-2058","authenticated-orcid":false,"given":"Rhiannon E. H.","family":"Jones","sequence":"first","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"Chang","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal","family":"Desai","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Hughes","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Jordan","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin M.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-9024","authenticated-orcid":false,"given":"Jonathan","family":"Latham","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Manning","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Melby","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Roerden","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaogong","family":"Su","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Whitten","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Honicker","sequence":"additional","affiliation":[{"name":"Drug Substance Development Drug Development and Supply GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacsau.2c00712"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cssc.202102709"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6GC02328B"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.7b02686"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-017-2395-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00437"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-018-0055-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm5018237"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901188v"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.7b00235"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/op2000783"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c07143"},{"key":"e_1_2_8_14_1","unstructured":"U. S.Pat. A.Stewart A. J.Toto F. X.Chen andG.Wu Methods of Manufacturing of Niraparib US11629137B2 2021."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcatb.2009.05.006"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c05175"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201400217"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/op400233z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.0c05450"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41929-019-0341-4"},{"key":"e_1_2_8_21_1","unstructured":"Further details about the sequences of the evolved variants are disclosed in patent.K. J.Honicker J. M.Kaplan J.Latham J.Melby C. W.Morgan andQ.Su Biocatalysts and Methods Thereof WO2024044657A1 2023."},{"key":"e_1_2_8_22_1","unstructured":"M.Quintanar\u2010Audelo E.Eberhard J.Nazor D.Smith andC.Wang EP2961844 2014."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.3c00941"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1188934"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cssc.200700168"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70508","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.70508","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:43:27Z","timestamp":1792043007000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.70508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":24,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,9,28]]}},"alternative-id":["10.1002\/cbic.70508"],"URL":"https:\/\/doi.org\/10.1002\/cbic.70508","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2026-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70508"}}