Histidine operon control

Figure 1-5-3. Attenuation Control of Transcription in the Histidine Operon...

The histidine operon consists of an operator region followed by the genes coding for the enzymes of histidine biosynthesis. The genes are transcribed into a single polycistronic messenger RNA, so that enzyme activities are controlled in a coordinate fashion. Transcription of the DNA code into mRNA, and probably also translation of the mRNA... 

Study of the repression control of the histidine operon has suggested that it may be more complicated than the model proposed by Jacob and Monod. This possibility is predicated on failure to find a pure repressor gene. This failure has left open the possibility that control may be exerted by aminoacylated tRNA alone, possibly at the level of protein synthesis rather than mRNA synthesis. Alternatively, the repressor could be encoded by one of the regulatory genes discussed, but could also serve an additional function vital to the cell. The necessity of maintaining this second function would prevent the isolation of mutants which had totally lost repressor activity. In line with this latter possibility, the complex of histidyl-tRNA synthetase with aminoacylated tRNA may serve as the repressor. The mutual affinity of these two macromolecules and their concentrations within the cell are such that a large portion of the aminoacylated tRNA may be complexed to the synthetase [20,118a]. 

Regulation of the Histidine Operon Translation-Controlled Transcription Termination (A Mechanism Common to Several Biosynthetic Operons)... 

Fig. 28. Four possible models of protein synthesis under the control of polycistron op-erons. The histidine operon is shown at the top of the scheme. Capital letters denote genes (cistrons) controlling histidine biosynthesis. DNA is represented as a double helix messenger RNA as straight lines of different lei ths ribosomes as small black circles and proteins as larger black circles. The time scale is indicated in the bottom left comer of the scheme (Goldberger and Berberich, 1966).

Other Systems - Other attenuation-controlled operons of "stalling sequences" include operons for synthesis of leucine, with four adjacent leucine codons in the leader sequence, and of histidine, with... 

Represslble Biosynthetic Systems. In enteric bacteria the represslble systems for histidine and tryptophan biosynthesis provide examples of systems controlled by positive and negative elements, respectively (see Table IV). Since the level of histidine In the colon Is among the lowest of all amino acids, expression of the histidine biosynthetic operon In the bacterium will be In hl demand (Table III). Thus, demand theory predicts that the histidine biosynthetic operon will be positively regulated (Table II). In fact, there Is good evidence to show that this operon Is controlled primarily by an antiterminator mechanism (, ). On the other hand, the level of tryptophan In the colon Is among the hipest of the amino acids and, therefore, expressl( i of the tryptophan biosynthetic operon In the bacterium... 

Another control over termination that has been extensively studied is the attenuation of transcription at the end of the leader regions of several amino acid biosynthetic operons (or genes) in E. coVl and related organisms (39). The primary indication that such a mechanism is involved in the control of an amino acid biosynthetic pathway is an endproduct repression that is dependent on the amino acid being transferred to its cognate tRNA at an ample rate. Thus, derepression of the histidine biosynthetic pathway can be achieved by any mechanism that reduces the intracellular level of histidyl tRNA, for example, by limiting the supply of histidine itself or by limiting the activity of the histidyl tRNA synthetase (51). 

This review has pointed out that the major control element in histidine production is feedback inhibition of the first enzyme of the pathway. However, most of the work on regulation of the operon has been devoted to repression control. This is partly because less is known about... 

If on the basis of the studies of mutants, one places all the segments of the operon in sequence as they appear in the chromosome, the sequence of Table 2-7 is obtained. Although the genes controlling histidine synthesis are arranged in a cluster, they are clearly not inserted in the operon in a sequence that corresponds to the sequence of steps in the metabolic pathway. 

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