Abstract: This invention describes novel methods for the identification of compounds useful as inhibitors of enzymes. The methods involve obtaining a target gene-complemented microorganism which is dependent on the expression of the target gene for survival in test conditions. By measuring the viability of the complemented microorganism after exposure to a compound, compounds that inhibit growth in test conditions are identified. These compounds that inhibit growth are further tested in conditions where the expression of the target gene is not required for growth in order to identify compounds that specifically inhibit the target gene but do not effect the viability of the host.