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This often leads to differences in productivity of the full\u2010scale process compared with laboratory scale. In this scale\u2010down study of penicillin production, the influence of substrate gradients on process performance and cell physiology was investigated by imposing an intermittent feeding regime on a laboratory\u2010scale culture of a high yielding strain of <jats:italic>Penicillium chrysogenum.<\/jats:italic> It was found that penicillin production was reduced by a factor of two in the intermittently fed cultures relative to constant feed cultivations fed with the same amount of glucose per hour, while the biomass yield was the same. Measurement of the levels of the intermediates of the penicillin biosynthesis pathway, along with the enzyme levels, suggested that the reduction of the flux through the penicillin pathway is mainly the result of a lower influx into the pathway, possibly due to inhibitory levels of adenosine monophosphate and pyrophosphate and lower activating levels of adenosine triphosphate during the zero\u2010substrate phase of each cycle of intermittent feeding.<\/jats:p>","DOI":"10.1002\/biot.201000409","type":"journal-article","created":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T04:36:30Z","timestamp":1309494990000},"page":"944-958","source":"Crossref","is-referenced-by-count":91,"title":["Scale\u2010down of penicillin production in <i>Penicillium chrysogenum<\/i>"],"prefix":"10.1002","volume":"6","author":[{"given":"Lodewijk P.","family":"de Jonge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas A. 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