Eventually it was discovered that two additional operators are involved in lac regulation.  One (O 3 ) lies about -90 bp upstream of O 1 in the end of the lacI gene, and the other (O 2 ) is about +410 bp downstream of O 1 in the early part of lacZ . These two sites were not found in the early work because they have redundant functions and individual mutations do not affect repression very much. Single mutations to either O 2 or O 3 have only 2 to 3-fold effects. However, their importance is demonstrated by the fact that a double mutant defective in both O 2 and O 3 is dramatically de-repressed (by about 70-fold).
Discovered in 1953 by Jacques Monod and colleagues, the trp operon in E. coli was the first repressible operon to be discovered. While the lac operon can be activated by a chemical ( allolactose ), the tryptophan (Trp) operon is inhibited by a chemical (tryptophan). This operon contains five structural genes: trp E, trp D, trp C, trp B, and trp A, which encodes tryptophan synthetase . It also contains a promoter which binds to RNA polymerase and an operator which blocks transcription when bound to the protein synthesized by the repressor gene (trp R) that binds to the operator. In the lac operon, lactose binds to the repressor protein and prevents it from repressing gene transcription, while in the trp operon, tryptophan binds to the repressor protein and enables it to repress gene transcription. Also unlike the lac operon, the trp operon contains a leader peptide and an attenuator sequence which allows for graded regulation.  This is an example of the corepressible model.