Expression of the Leucine Operon

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Abstract
The four genes which specify the structure of the three enzymes specifically involved in the biosynthesis of leucine in Salmonella typhimurium constitute a single operon. Three types of control mutants have been delineated on the basis of their location on the Salmonella chromosome and the manner in which they coordinately affect the rates of synthesis of the pertinent enzymes. The three types of mutants correspond to operator-negative, operator-constitutive, and regulator-negative. The rate of synthesis of the enzymes can also be altered by varying the amount of leucine made available to the cell. Leucine can be effectively limited by limiting the supply of [alpha]-ketoisovalerate, but in doing so two of the three enzymes, [alpha]-iso-propylmalate synthetase and isopropylmalate isomerase, are labilized. This observation was correlated with an in vivo diminution of the levels of the substrates of these enzymes and the fact that [alpha]-ketoisovalerate and [alpha]-isopropylmalate protect the respective enzymes against thermal inactivation in vitro. The functional association of the structural genes is also illustrated by the presence of polarity mutations; that is, certain structural gene mutations lower the rates of synthesis of the enzymes specified by genes located distally to the mutated gene and the operator segment of the operon.

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