The design of these methods requires some basic understanding of the product metabolism and pathway regulation. This knowledge can be used to propose environmental conditions, or the addition of a chemi- cal that could be a chromogenic or selective reagent, a dye or an indicator organism. For example, a toxic precursor of penicillin (phenylacetic acid) was added to the agar medium, where the sensitive parent strains were prevented from growing, while only resistant mutants propagated. In this case, 16.7% of the resis- tant mutants produced more antibiotic than the pa- rental strain (Barrios-Gonzalez et al, 1993b).