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It was found that at 400 RPM applied in prolonged glucose\u2010limited chemostat cultures, the previously reported degeneration of penicillin production using an industrial <jats:italic>Penicillium chrysogenum<\/jats:italic> strain was virtually absent. To investigate this, the cellular response was studied at flux (stoichiometry), residual glucose, intracellular metabolite and transcript levels. At 600 RPM, 20% more cell lysis was observed and the increased degeneration of penicillin production was accompanied by a 22% larger ATP gap and an unexpected 20\u2010fold decrease in the residual glucose concentration (<jats:italic>C<\/jats:italic><jats:sub>s,out<\/jats:sub>). At the same time, the biomass specific glucose consumption rate (<jats:italic>q<\/jats:italic><jats:sub>s<\/jats:sub>) did not change but the intracellular glucose concentration was about sixfold higher, which indicates a change to a higher affinity glucose transporter at 600 RPM. In addition, power input differences cause differences in the diffusion rates of glucose and the calculated Batchelor diffusion length scale suggests the presence of a glucose diffusion layer at the glucose transporting parts of the hyphae, which was further substantiated by a simple proposed glucose diffusion\u2010uptake model. By analysis of calculated mass action ratios (MARs) and energy consumption, it indicated that at 600 RPM glucose sensing and signal transduction in response to the low <jats:italic>C<\/jats:italic><jats:sub>s,out<\/jats:sub> appear to trigger a gluconeogenic type of metabolic flux rearrangement, a futile cycle through the pentose phosphate pathway (PPP) and a declining redox state of the cytosol. In support of the change in glucose transport and degeneration of penicillin production at 600 RPM, the transcript levels of the putative high\u2010affinity glucose\/hexose transporter genes <jats:italic>Pc12g02880<\/jats:italic> and <jats:italic>Pc06g01340<\/jats:italic> increased 3.5\u2010 and 3.3\u2010fold, respectively, and those of the <jats:italic>pcbC<\/jats:italic> gene encoding isopenicillin N\u2010synthetase (IPNS) were more than twofold lower in the time range of 100\u2013200\u2009hr of the chemostat cultures. Summarizing, changes at power input have unexpected effects on degeneration and glucose transport, and result in significant metabolic rearrangements. These findings are relevant for the industrial production of penicillin, and other fermentations with filamentous microorganisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bit.26447","type":"journal-article","created":{"date-parts":[[2017,9,2]],"date-time":"2017-09-02T06:36:36Z","timestamp":1504334196000},"page":"114-125","source":"Crossref","is-referenced-by-count":22,"title":["Power input effects on degeneration in prolonged penicillin chemostat cultures: A systems analysis at flux, residual glucose, metabolite, and transcript levels"],"prefix":"10.1002","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-3054","authenticated-orcid":false,"given":"Guan","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology (ECUST) Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baofeng","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology (ECUST) Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfei","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology (ECUST) Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cees","family":"Haringa","sequence":"additional","affiliation":[{"name":"Transport Phenomena, Chemical Engineering Department Delft University of Technology Delft The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianye","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology (ECUST) Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6406-1748","authenticated-orcid":false,"given":"Ju","family":"Chu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology (ECUST) Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingping","family":"Zhuang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology (ECUST) Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology (ECUST) Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph J.","family":"Heijnen","sequence":"additional","affiliation":[{"name":"Cell Systems Engineering, Department of Biotechnology Delft University of Technology Delft The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"van Gulik","sequence":"additional","affiliation":[{"name":"Cell Systems Engineering, Department of Biotechnology Delft University of Technology Delft The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit T.","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"DSM Biotechnology Center Delft The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk J.","family":"Noorman","sequence":"additional","affiliation":[{"name":"DSM Biotechnology Center Delft The Netherlands"},{"name":"Bio Process Engineering, Department of Biotechnology Delft University of Technology Delft The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(19990220)62:4<434::AID-BIT6>3.0.CO;2-D"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-703X(99)00059-5"},{"issue":"13","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1016\/S0021-9258(18)95956-9","article-title":"Adenosine triphosphate conservation in metabolic regulation rat liver citrate cleavage enzyme","volume":"242","author":"Atkinson D. 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