Penicillin: VIII. Production of Penicillin in Surface Cultures.

The production of penicillin by the surface culture of Penicillium notatum is the foundation upon which a large new industry has been built. Although cultivation of the mold in submerged culture now appears to be more economical and more practical from an industrial standpoint, surface cultures were utilized to produce the penicillin that first effected the remarkable clinical cures which indicated that the large investment of time and money made during the past three years would be justified. Previous investigators of penicillin production have not been successful in developing a highly productive medium. Fleming (1929), the discoverer of the drug, refers only to the use of a "nutrient broth," whereas Clutterbuck, Lovell, and Raistrick (1932) used a modified Czapek-Dox medium. Although the yields of penicillin obtained by this group and by Fleming were not evaluated in terms of the Oxford unit adopted later, they were undoubtedly very low, at least when compared with present standards. Abraham et al. (1941), using the same modified Czapek-Dox medium with the addition of small amounts of a crude yeast extract, obtained only 2 to 6 Oxford units per ml. This paper will report on a few of more than five hundred experiments which have led to an increase in the yield of penicillin from the range of 2 to 6 Oxford units per ml to as much as 160 to 220 Oxford units per ml. This increase in yield has been achieved primarily by the proper selection of organisms and nutrients, including the use of corn steep liquor, the use of lactose as the principal carbohydrate, and the addition of nutrients during the course of the fermentation.3