Although the natural penicillins are excellent antibiotics, their properties depend on the side chain. For example, simply changing the side chain to the phenoxymethyl of Penicillin V confers much better acid stability so that oral administration is not so badly beset by the low pH in the stomach. In other words, Penicillin V has relatively good acid stability. A great advance was using the enzyme penicillin acylase to cleave off the side chain.
Commercial manufacturing relies on immobilizing the enzyme for economic reuse.