{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:26:37Z","timestamp":1790717197382,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T00:00:00Z","timestamp":1439942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TR 124"],"award-info":[{"award-number":["TR 124"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["01ZX1402C"],"award-info":[{"award-number":["01ZX1402C"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotech &amp;amp; Bioengineering"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>More than 80 years after its discovery, penicillin is still a widely used and commercially highly important antibiotic. Here, we analyse the metabolic network of penicillin synthesis in <jats:italic>Penicillium chrysogenum<\/jats:italic> based on the concept of elementary flux modes. In particular, we consider the synthesis of the invariant molecular core of the various subtypes of penicillin and the two major ways of incorporating sulfur: transsulfuration and direct sulfhydrylation. 66 elementary modes producing this invariant core are obtained. These show four different yields with respect to glucose, notably \u00bd, 2\/5, 1\/3, and 2\/7, with the highest yield of \u00bd occurring only when direct sulfhydrylation is used and \u03b1\u2010aminoadipate is completely recycled. In the case of no recycling of this intermediate, we find the maximum yield to be 2\/7. We compare these values with earlier literature values. Our analysis provides a systematic overview of the redundancy in penicillin synthesis and a detailed insight into the corresponding routes. Moreover, we derive suggestions for potential knockouts that could increase the average yield. Biotechnol. Bioeng. 2016;113: 173\u2013181. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bit.25694","type":"journal-article","created":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T01:11:03Z","timestamp":1435799463000},"page":"173-181","source":"Crossref","is-referenced-by-count":10,"title":["Computing the various pathways of penicillin synthesis and their molar yields"],"prefix":"10.1002","volume":"113","author":[{"given":"Maria T. E.","family":"Prau\u00dfe","sequence":"first","affiliation":[{"name":"Department of Bioinformatics University of Jena Ernst\u2010Abbe\u2010Pl. 2, 07743 Jena Germany"},{"name":"Leibniz\u2010Institute for Natural Product Research and Infection Biology \u2013 Hans\u2010Kn\u00f6ll\u2010Institute Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Sch\u00e4uble","sequence":"additional","affiliation":[{"name":"Jena University Language &amp; Information Engineering Lab Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Guthke","sequence":"additional","affiliation":[{"name":"Leibniz\u2010Institute for Natural Product Research and Infection Biology \u2013 Hans\u2010Kn\u00f6ll\u2010Institute Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schuster","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics University of Jena Ernst\u2010Abbe\u2010Pl. 2, 07743 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002980"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2007.09.043"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0381286"},{"key":"e_1_2_6_5_1","first-page":"45","article-title":"Regulation of penicillin biosynthesis in filamentous fungi","volume":"88","author":"Brakhage AA","year":"2004","journal-title":"Adv Biochem Eng Biotechnol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2916"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.10803"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-005-0029-y"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1656(95)00056-V"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(20000620)68:6<652::AID-BIT8>3.0.CO;2-J"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260191004"},{"key":"e_1_2_6_12_1","first-page":"29","volume-title":"Biosynthesis of Antibiotics","author":"Demain AL","year":"1967"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-012-9852-z"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00173993"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01311-13"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307968200"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2012.08700.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2014.10.029"},{"key":"e_1_2_6_19_1","volume-title":"Fungal physiology","author":"Griffin DH","year":"1996"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260241002"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00387324"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.03.006"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00093-07"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jctb.280350107"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260211204"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260230715"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1656(95)00164-6"},{"key":"e_1_2_6_28_1","first-page":"45","volume-title":"Biotechnology and industrial antibiotics. Drugs and the pharmaceutical sciences","author":"Herschbach GJM","year":"1984"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-009-2168-4"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900327-MCP200"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260460205"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/0470015330"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(02)00034-3"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2006.02.001"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511977022"},{"key":"e_1_2_6_36_1","volume-title":"Physiological engineering aspects of Penicillium chrysogenum","author":"Nielsen J","year":"1996"},{"key":"e_1_2_6_37_1","volume-title":"Penicillinherstellung. Von den Anf\u00e4ngen bis zur Gro\u00dfproduktion","author":"Pieroth I","year":"1992"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(98)01229-3"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2859-11-88"},{"key":"e_1_2_6_40_1","first-page":"27","article-title":"Comparative study on production of penicillin by Penicillium notatum and Penicillium chrysogenum and its antimicrobial property","volume":"6","author":"Ratnam J","year":"2014","journal-title":"Int J Biotech Trends and Technol"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2010.07.002"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12009"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023026"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.2000.1073"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(98)01290-6"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004490100253"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-244-1_12"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03145"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061648"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.00577-14"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1006\/mben.2001.0218"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25498"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2006.07.006"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-008-1770-1"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2009.11.002"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1498"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0290(20000120)72:2<185::AID-BIT7>3.0.CO;2-M"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl267"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-S1-S11"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-010-9389-0"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-73-1-71"},{"key":"e_1_2_6_62_1","first-page":"5","volume-title":"Amino acid biosynthesis\u2014Pathways, regulation and metabolic engineering","author":"Wittmann C","year":"2007"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201200269"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbit.25694","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.25694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:21:36Z","timestamp":1759944096000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.25694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,19]]},"references-count":62,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1002\/bit.25694"],"URL":"https:\/\/doi.org\/10.1002\/bit.25694","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,19]]}}}