{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:42:54Z","timestamp":1788576174632,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The kinetics of cephalexin synthesis and hydrolysis of the activated acyl\u2010donor precursor phenylglycine methyl ester\u00a0(PGME) were characterized under a broad range of substrate concentrations. A previously developed model by Youshko\u2010Svedas involving the formation of the acyl\u2010enzyme complex followed by binding of the nucleophilic \u03b2\u2010lactam donor does not fully estimate the maximum reaction yields for cephalexin synthesis at different concentrations using initial\u2010rate data. 7\u2010aminodesacetoxycephalosporanic acid\u00a0(7\u2010ADCA) was discovered to be a potent inhibitor of cephalexin hydrolysis, which may account for the deviation from model predictions. Three kinetic models were compared for cephalexin synthesis, with the model incorporating competitive inhibition due to 7\u2010ADCA yielding the best fit. Additionally, the \u03b2F24A variant and Assemblase\u00ae did not exhibit significantly different kinetics for the synthesis of cephalexin compared to the wild\u2010type, for the concentration range evaluated and for both initial\u2010rate experiments and time\u2010course synthesis experiments. Lastly, a continuous stirred\u2010tank reactor for cephalexin synthesis was simulated using the model incorporating competitive inhibition by 7\u2010ADCA, with clear tradeoffs observed between productivity, fractional yield, and PGME conversion.<\/jats:p>","DOI":"10.1002\/bit.28214","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T09:19:41Z","timestamp":1661678381000},"page":"3117-3126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Selectivity and kinetic modeling of penicillin G acylase variants for the synthesis of cephalexin under a broad range of substrate concentrations"],"prefix":"10.1002","volume":"119","author":[{"given":"Patrick R.","family":"Harris","sequence":"first","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7036-776X","authenticated-orcid":false,"given":"Martha A.","family":"Grover","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4126-7153","authenticated-orcid":false,"given":"Ronald W.","family":"Rousseau","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-1675","authenticated-orcid":false,"given":"Andreas S.","family":"Bommarius","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.02857.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/13.12.857"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzh057"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03728.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70780-7"},{"key":"e_1_2_9_7_1","volume-title":"Model selection and multimodel inference: A practical information\u2010theoretic approach","author":"Burnham K. 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