|United States Of America||Issued Patent||9,540,652||01/10/2017||2011-079|
Investigators at UC Berkeley have developed an alternative approach to engineer the shikimate pathway in E. coli. The native pathway was reconstructed in a modular fashion to remove bottlenecks and optimize the flux and production by improving promoters and regulatory elements.
Using these modifications to the shikimate pathway resulted in strains that produce high yields of tyrosine and other valuable intermediates such as shikimate and dehydroshikimate and also dehydroquinate and quinate.
This pathway engineering can also be used for production of other aromatic amino acids, tryptophan and phenylalanine at high yields as well as additional intermediates such as phenylpyruvate, anthranilate, and others.
These constructed metabolic pathways can be transferred to other strains or microorganisms.
Previous work has tried to change only a few pathway enzymes at a time. This more systematic approach can better optimize flux in the pathway.
This invention puts all of the genes on together, simplifying the regulation and synthesis of new strains.
The constructed modules ca be transferred to other strains or microorganisms or even to the chromosomes to increase stability.
As a modular system, additional enzymes can be added to produce other amino acids or intermediates associated with the shikimate pathway.
This process did not result in growth inhibition as commonly observed in other reported attempts to improve pathway yield.