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Protocols often seem to use regulatable promoters when expressing a heterologous gene in a host like yeast where they add something like IPTG to induce expression from (say) the lac promoter.

Is there a reason to do this as opposed to using a constitutive promoter? i.e. Is there reason to think that regulatable (inducible) promoters have higher expression levels than constitutive promoters?

In other words, what utility is there in having an external "switch", i.e. the IPTG to turn on expression on-demand rather than just boost the default expression level using a promoter not requiring induction?

The goal here is small biomolecule synthesis by industrial fermentation of a transgenic yeast.

Example Protocol:

L21 Star™ (DE3) E. coli cells (Invitrogen) were co-transformed with the plasmids pACYCDuet-4506 and Ct94-pETDuet and transformed cells were selected on carbenicillin (50 μg/ml) chloramphenicol (34 μg/ml) LB-agarose plates. Single colonies were used to inoculate 5 mL LB medium with 50 μg/ml carbenicilin and 34 μg/ml chloramphenicol. The culture was incubated overnight at 37° C. The next day 2 mL of TB medium supplemented with the same antibiotics were inoculated with 0.2 mL of the overnight culture. After 6 hours incubation at 37° C., the culture was cooled down to 28° C. and 1 mM IPTG, 2 mg/mL mevalonate (prepared by dissolving mevalonolactone (Sigma) in 0.5N NaOH at a concentration of 1 g/mL and incubating the solution for 30 minutes at 37° C.) and 0.2 mL decane were added to each tube. The cultures were incubated for 48 hours at 28° C. The cultures were then extracted twice with 2 volumes of ethyl acetate, the organic phase was concentrated to 500 μL and analyzed by GC-MS as described above in Example 3. In these conditions sesquiterpene production above 200 mg/L was routinely achieved. Beta-santalene was produced.

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    $\begingroup$ This sounds an awful lot like a homework or quiz question. As such you need to show your effort to answer the question. Please refer to Biology S.E help center for information and policies on asking questions on the site. These links, biology.stackexchange.com/help/how-to-ask , biology.stackexchange.com/help/on-topic , and biology.stackexchange.com/help/dont-ask are particularly helpful. $\endgroup$ – AMR Jul 5 '16 at 5:43
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    $\begingroup$ @AMR I'm not sure why you think this is a Homework question & I'm also not sure how to convince you that it is not. In any case, if it helps I am working on a feasibility study to industrially manufacture a 250 MW secondary metabolite which is currently only available as a plant extract. The wild type gene responsible has been sequenced. The native expression is low, <50 mg/L mostly because of bottlenecks in making FPP the precursor & FPP-sinks via Squalene. $\endgroup$ – curious_cat Jul 5 '16 at 5:49
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    $\begingroup$ Inducible promotors are a useful tool especially in experiments where the inserted/altered gene may needs to be suppressed at first. Consider an experiment where one wishes to investigate a putative Alzheimer-inducing gene in a model of old age. When you insert the exogeneous/altered gene, you may wish to suppress expression up until the point where your animals reach a sufficiently old age to mimick geriatric patients developing Alzheimer symptoms. Another example is where one uses genes that are lethal or induce gross developmental changes in utero when expressed during development. $\endgroup$ – AliceD Jul 6 '16 at 20:20
  • $\begingroup$ @Christiaan Makes sense. I was just wondering about my industrial fermentation use-case where all I want to do is maximize the yield of a secondary metabolite. $\endgroup$ – curious_cat Jul 7 '16 at 5:24
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Heterologous promoters often express genes that are toxic to the organism when expressed in too high quantities. When the genes are expressed constitutively, the organism will either grow slowly or die before they reach a high density suitable for production of the protein.

As such, it is not about expressing the genes all the time, but expressing the maximum amount of gene product over the shortest period of time. It doesn't make sense for the cells to express the gene product all the time, if they can't reach sufficient densities first. More product will be made if the cells are allowed to grow to a relatively high density, then inducing expression on all of them. This would allow relatively large production levels in a short period of time.

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    $\begingroup$ Perfect! This explanation makes a lot of sense. This is exactly the part I was missing in my understanding. This totally justifies using induction. $\endgroup$ – curious_cat Jul 5 '16 at 7:16

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