Andrew Moyer replaced sucrose with lactose in the penicillin growth medium.
The change was made during the U.S. penicillin-production effort at the Northern Regional Research Laboratory in Peoria, Illinois, in 1941. The Oxford team’s earlier culture medium used sucrose, but Moyer tested alternative carbohydrates to find conditions that would improve mould growth and penicillin formation.
Lactose proved especially useful because the mould metabolized it more slowly than sugars such as glucose or sucrose. That slower utilization helped maintain the kind of nutrient conditions associated with sustained penicillin production. Lactose was not the antibiotic and did not chemically become penicillin; it served as a carbon source in the culture medium.
This detail is sometimes muddled because later accounts also mention replacing glucose with lactose, and industrial recipes could contain more than one carbohydrate. In the specific historical comparison asked here, however, Moyer’s replacement was sucrose with lactose. The lactose substitution was followed by the even larger breakthrough of adding corn steep liquor.