Increasing the yield of penicillin
Orville May, Director of the NRRL, agreed to have the Laboratory undertake a vigorous program to increase penicillin
yields under the direction of Robert Coghill, Chief of the Fermentation Division. It was agreed that Heatley would remain
in Peoria to share his expertise with his American colleagues. Within a few weeks, Andrew Moyer found that he could
significantly increase the yield of penicillin by substituting lactose for the sucrose used by the Oxford team in their
culture medium. Shortly thereafter, Moyer made the even more important discovery that the addition of corn-steep liquor to
the fermentation medium produced a ten-fold increase in yield. Corn-steep liquor was a by-product of the corn wetmilling
process, and the NRRL, in an attempt to find a use for it, tried it in essentially all of its fermentation work. Later,
the Peoria laboratory increased the yield of penicillin still further by the addition of penicillin precursors, such as
phenylacetic acid, to the fermentation medium.
It was recognized that the Oxford group's method of growing the mold on the surface of a nutrient medium was inefficient,
and that growth in submerged culture would be a superior process. In submerged culture fermentation, the mold is grown in large
tanks in a constantly agitated and aerated mixture, rather than just on the surface of the medium. Florey's Penicillium culture,
however, produced only traces of penicillin when grown in submerged culture. Under the direction of Kenneth Raper, staff at the
NRRL screened various Penicillium strains and found one that produced acceptable yields of penicillin in submerged culture. Soon a
global search was underway for better penicillin producing strains, with soil samples being sent to the NRRL from around the world.
Ironically, the most productive strain came from a moldy cantaloupe from a Peoria fruit market. A more productive mutant of the
so-called cantaloupe strain was produced with the use of X-rays at the Carnegie Institution. When this strain was exposed to
ultraviolet radiation at the University of Wisconsin, its productivity was increased still further.