{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:44Z","timestamp":1788912044086,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T00:00:00Z","timestamp":1563148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>During glucose\u2010limited growth, a substantial input of adenosine triphosphate (ATP) is required for the production of \u03b2\u2010lactams by the filamentous fungus <jats:italic>Penicillium chrysogenum<\/jats:italic>. Formate dehydrogenase has been confirmed in <jats:italic>P. chrysogenum<\/jats:italic> for formate oxidation allowing an extra supply of ATP, and coassimilation of glucose and formate has the potential to increase penicillin production and biomass yield. In this study, the steady\u2010state metabolite levels and fluxes in response to cofeeding of formate as an auxiliary substrate in glucose\u2010limited chemostat cultures at the dilution rates (<jats:italic>D<\/jats:italic>) of both 0.03\u2009h<jats:sup>\u22121<\/jats:sup> and 0.05\u2009h<jats:sup>\u22121<\/jats:sup> are determined to evaluate the quantitative impact on the physiology of a high\u2010yielding <jats:italic>P. chrysogenum<\/jats:italic> strain. It is observed that an equimolar addition of formate is conducive to an increase in both biomass yield and penicillin production at <jats:italic>D<\/jats:italic>\u2009=\u20090.03\u2009h<jats:sup>\u22121<\/jats:sup>, while this is not the case at <jats:italic>D<\/jats:italic>\u2009=\u20090.05\u2009h<jats:sup>\u22121<\/jats:sup>. In addition, a higher cytosolic redox status (NADH\/NAD<jats:sup>+<\/jats:sup>), a higher intracellular glucose level, and lower penicillin productivity are only observed upon formate addition at <jats:italic>D<\/jats:italic>\u2009=\u20090.05\u2009h<jats:sup>\u22121<\/jats:sup>, which are virtually absent at <jats:italic>D<\/jats:italic>\u2009=\u20090.03\u2009h<jats:sup>\u22121<\/jats:sup>. In conclusion, the results demonstrate that the effect of formate as an auxiliary substrate on penicillin productivity in the glucose\u2010limited chemostat cultivations of <jats:italic>P. chrysogenum<\/jats:italic> is not only dependent on the formate\/glucose ratio as published before but also on the specific growth rate. The results also imply that the overall process productivity and quality regarding the use of formate should be further explored in an actual industrial\u2010scale scenario.<\/jats:p>","DOI":"10.1002\/biot.201900009","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T08:22:01Z","timestamp":1559118121000},"source":"Crossref","is-referenced-by-count":13,"title":["Comparative Fluxome and Metabolome Analysis of Formate as an Auxiliary Substrate for Penicillin Production in Glucose\u2010Limited Cultivation of <i>Penicillium chrysogenum<\/i>"],"prefix":"10.1002","volume":"14","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)  130 Meilong Road Shanghai 200237 P. R. 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