Metabolic transistor in bacteria
AssigneeWilliam Marsh Rice University
InventorsKa-Yiu SAN, George N. BENNETT, Hui WU
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Abstract
The disclosure relates to a metabolic transistor in microbes such as bacteria and yeast where a competitive pathway is introduced to compete with a product pathway for available carbon so as to control the carbon flux in the microbe.
Claims23
1) A method of increasing the production of a product in a microbe, said method comprising:
- a) providing a microbe having a product pathway producing a product, wherein a competitive pathway competes with said product pathway for available carbon, said competitive pathway requiring a cofactor that is not rate limiting and not used in said product pathway;
- b) adding one or more diverting gene(s) under the control of a promoter to said microbe to directly or indirectly divert said cofactor away from said competitive pathway;
- and,
- c) allowing expression of said diverting gene(s) and reducing levels of said cofactor, and thus reducing levels of said competitive pathway;
- d) thereby increasing said product pathway and said product.
6) A method of controlling aerobic respiration in a microbe in the presence of O2, said method comprising:
- a) adding a diverting gene(s) to a microbe to divert substrates away from ubiquinone or thiamine or heme production, wherein said diverting gene(s) is under the control of a promoter;
- and,
- b) inducing said promoter, thereby allowing expression of said diverting gene(s), thus reducing ubiquinone levels and reducing aerobic respiration in the presence of 02.
13) A method of producing a product in a microbe, comprising:
- a) growing a microbe capable of producing a product in cell culture under aerobic conditions;
- i) said microbe comprising a diverting gene(s) added to said microbe to divert a cofactor away from an electron transport chain, wherein said diverting gene(s) is under the control of an inducible promoter;
- b) inducing said promoter, thereby allowing expression of said diverting gene(s), thus reducing cofactors levels and reducing aerobic respiration in the presence of O2 and thereby driving carbons towards production of said product;
- and,
- c) isolating said product.
21) A microbial cell engineered to allow fine control over production of a product, wherein a diverting gene(s) has been added to said micobe, wherein said diverting gene(s) allows the diversion of a key intermediate of a competitive pathway, thus allowing fine control of said competitive pathway including said key intermediate, and increased production of a product not requiring said key intermediate.
Dependencies are inferred from the claim text.