Metabolic transistor in bacteria

Patent metadata

Field	Value
Publication number	US-9441253-B2
Application number	US-201414176008-A
Country	US
Kind code	B2
Filing date	Feb 7, 2014
Priority date	Feb 11, 2013
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

The disclosure relates to a metabolic transistor in bacteria where a competitive pathway is introduced to compete with a product pathway for available carbon so as to control the carbon flux in the bacteria.

First claim

We claim:

1. A method of increasing the production of a product in a bacteria, said method comprising:
a) providing a bacteria 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;
b) introducing one or more diverting gene(s) under the control of a promoter into said bacteria to directly or indirectly divert said cofactor or an intermediate in the formation of the cofactor away from said competitive pathway;
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;
wherein said cofactor and said one or more diverting genes and said products are selected from the group consisting of:

Cofactor:
Diverting gene(s) encoding:
Product:

ubiquinone
geranylgeranyl diphosphate
Fermentative products or

synthase and phytoene
lactate or acetate ethanol or

synthase and phytoene
formate, or acetate or

desaturase
succinate or 2,3 butane diol

ubiquinone
geranyl diphosphate: 4-
Fermentative products or

hydroxybenzoate
lactate or acetate ethanol or

geranyltransferase
formate, or acetate or

succinate or 2,3 butane diol

biotin
Biotin-CoA ligase or biotin
Glutamate or lysine

CoA synthetase

pantothenate
pantothenate hydrolyase
Valine

thiamine
thiamine pyridinylase or
Fermentative products or

aminopyrimidine
lactate or ethanol or formate,

aminohydrolase
or acetate or succinate or 2,3

butane diol pr

Folate or 4-
4-aminobenzoate 1-
Serine

amino-
monooxygenase or

benzoate
aminobenzoate

decarboxylase

Heme
Siroheme synthase
Fermentative products or

lactate or acetate ethanol or

formate or acetate or succinate

or 2,3 butane diol

3-Methyl-2-
2-oxoisovalerate
PHE or TYR.

oxobutanoic
dehydrogenase or 3-methyl-

acid
2-oxobutanoate

dehydrogenase

2. The method of claim 1 , wherein said promoter is a constitutive promoter.

3. The method of claim 1 , wherein said promoter is an inducible promoter.

4. The method of claim 1 , wherein said bacteria is E. coli or Corynebacterium glutamicum.

5. The method of claim 1 , wherein said cofactor is ubiquinone and said diverting gene(s) is i) crtE, crtB and crtI or ii) PGT-1.

6. The method of claim 1 , wherein said cofactor is heme and said diverting gene(s) encodes siroheme synthase.

7. The method of claim 1 , wherein said cofactor is thiamine and said diverting gene(s) encodes thiamine pyridinylase or aminopyrimidine aminohydrolase.

Assignees

• Univ Rice William M

Inventors

• San Ka-Yiu
• Bennett George N
• Wu Hui

Classifications

• C12P7/065

  with microorganisms other than yeasts · CPC title

• C12N9/93

  Ligases (6) · CPC title

• C12Y401/01024

  Aminobenzoate decarboxylase (4.1.1.24) · CPC title

• Y02E50/17

  Cross-Sectional Technologies · mapped topic

• C12Y602/01011

  Biotin--CoA ligase (6.2.1.11) · CPC title