{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:32:11Z","timestamp":1786977131567,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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>\n                  <jats:p>\n                    7\u2010Methylxanthine, a derivative of caffeine (1,3,7\u2010trimethylxanthine), is a high\u2010value compound that has multiple medical applications, particularly with respect to eye health. Here, we demonstrate the biocatalytic production of 7\u2010methylxanthine from caffeine using\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    strain MBM019, which was constructed for production of paraxanthine (1,7\u2010dimethylxanthine). The mutant\n                    <jats:italic>N<\/jats:italic>\n                    \u2010demethylase NdmA4, which was previously shown to catalyze\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sub>3<\/jats:sub>\n                    \u2010demethylation of caffeine to produce paraxanthine, also retains\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    \u2010demethylation activity toward paraxanthine. This study demonstrates that whole cell biocatalysts containing NdmA4 are more active toward paraxanthine than caffeine. We used four serial resting cell assays, with spent cells exchanged for fresh cells between each round, to produce 2,120\u2009\u03bcM 7\u2010methylxanthine and 552\u2009\u03bcM paraxanthine from 4,331\u2009\u03bcM caffeine. The purified 7\u2010methylxanthine and paraxanthine were then isolated via preparatory\u2010scale HPLC, resulting in 177.3\u2009mg 7\u2010methylxanthine and 48.1\u2009mg paraxanthine at high purity. This is the first reported strain genetically optimized for the biosynthetic production of 7\u2010methylxanthine from caffeine.\n                  <\/jats:p>","DOI":"10.1002\/bit.28212","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T02:25:40Z","timestamp":1662344740000},"page":"3326-3331","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Biocatalytic production of 7\u2010methylxanthine by a caffeine\u2010degrading\n                    <i>Escherichia coli<\/i>\n                    strain"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5316-1575","authenticated-orcid":false,"given":"Meredith B.","family":"Mock","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Cyrus","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1358-6605","authenticated-orcid":false,"given":"Ryan M.","family":"Summers","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-015-0395-1"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcab.2017.06.014"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.31699\/IJCPE.2020.3.3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2009.01688.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22337"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13030803"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.08.004"},{"issue":"1","key":"e_1_2_6_9_1","first-page":"16\u2010","article-title":"Differential effect of selected methylxanthine derivatives on radiosensitization of lung carcinoma cells","volume":"28","author":"Malki A.","year":"2006","journal-title":"Experimental oncology"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2016.08.003"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.12.17.472166"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","unstructured":"Mock M. B. Mills S. B. Cyrus A. Campo H. Dreischarf T. Strock S. &Summers R. M.(2022).Biocatalytic production and purification of the high\u2010value biochemical paraxanthine.Biotechnology and Bioprocess Engineering 1\u201312.https:\/\/doi.org\/10.1007\/s12257-021-0301-0","DOI":"10.1007\/s12257-021-0301-0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotno.2021.05.001"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3980\/j.issn.2222-3959.2012.02.03"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2018.e00829"},{"key":"e_1_2_6_16_1","volume-title":"The caffeine analogue, 1\u2010hexyl\u20103\u2010propyl\u20107\u2010methylxanthine inhibits malignant transformation and stimulates apoptosis and intracellular cAMP content in JB6 cells","author":"Rogozin E. 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