Some chemicals, when added to certain fermentations, are directly incorporated into the desired product. Probably the earliest example is that of improving penicillin yields. A range of different side chains can be incorporated intothe penicillin molecule. The significance of the different side chains was first appreciated when it was noted that the addition of corn-steep liquor increased the yield of penicillin from 20 units cm- 3 to 100 units cm- 3. Corn-steep liquor was found to contain phenylethylamine which was preferentially incorporated into the penicillin molecule to yield benzyl penicillin (Penicillin G). Having established that the activity of penicillin lay in the side chain, and that the limiting factor was the synthesis of the side chain, it became standard practice to add side-chain precursors to the medium, in particular phenylacetic acid. Smith and Bide (1948) showed that addition of phenylacetic acid and its derivatives to the medium were capable of both increasing penicillin production threefold and to directing biosynthesis towards increasing the proportionof benzyl penicillin from 0 to 93% at the expenseof other penicillins. Phenylacetic acid is still the most widely used precursor in penicillin production. Some important examples of precursors are given in Table 4.12.