Microbiological Aspects of Penicillin: III. Production of Penicillin in Surface Cultures of Penicillium notatum.

Steadily increasing interest in penicillin as a chemotherapeutic agent has led to a parallel increase in the demand for penicillin for clinical application and chemical studies. Penicillin is produced in minute quantities by Penicillium notatum so that filtrates from the mold represent exceedingly dilute solutions of penicillin from which the active agent is extracted. The magnitude of the problem may be illustrated by the experience of the Oxford workers (Abraham, et al., 1941). From 3 to 5 grams of crude penicillin which, on the basis of a later publication (Abraham, Chain and Holiday, 1942), could be at best only approximately 5 per cent pure, was required for a single clinical treatment, such an amount requiring the extraction of 300 to 500 liters of P. notatum filtrate. The extreme lability of penicillin lends additional complexities to the production of the active substance. Aside from the report by the Oxford investigators (Abraham, et al., 1941), little information pertaining directly to the microbiological aspects of penicillin production has appeared (see also Challinor, 1942; Clutterbuck, et al., 1932; Fleming, 1929, 1932; Foster and Wilker, 1943; Foster and Woodruff, 1943; Hobby, et al., 1942; Kocholaty, 1942; Reid, 1935). This paper presents some general characteristics of the production of penicillin and their relation to the metabolism of P. notatum. Estimation of penicillin potencies were for the most part made by the modified Oxford cup method (Foster and Woodruff, 1943). In a few cases the dilution method was used.