Methods and organisms with increased carbon flux efficiencies

Abstract

The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.

1 . A non-naturally occurring microbial organism comprising a genetic alteration selected from the group consisting of:
 (1) attenuation of cydA or cydB, and one or more of a genetic alteration selected from the group consisting of:
 (a) a genetic alteration that increases expression of a protein encoded by pntAB; 
 (b) attenuation of the protein encoded by pykF; 
 (c) attenuation of the protein encoded by sucCD; 
 (d) attenuation of the protein encoded by yciA; 
 (e) a genetic alteration that increases expression of a protein encoded by ackA and a protein encoded by pta; 
 (f) a genetic alteration that increases expression of a protein encoded by cyoB; 
 (g) attenuation of the protein encoded by pykA; 
 (h) attenuation of the protein encoded by arcA; 
 (i) attenuation of the protein encoded by crr; 
 (j) attenuation of the protein encoded by clpA; and 
 (k) attenuation of the protein encoded by menC; and 
   (2) a genetic alteration selected from the group consisting of
 (a) attenuation of the proteins encoded by sucCD and yciA; 
 (b) attenuation of the proteins encoded by sucCD and yciA, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (c) attenuation of the proteins encoded by sucCD and yciA, and having a genetic alteration that increases expression of a protein encoded by cyoB; 
 (d) attenuation of the proteins encoded by sucCD, yciA and cydA or cydB, and having a genetic alteration that increases expression of a protein encoded by cyoB; 
 (e) attenuation of the proteins encoded by sucCD, yciA and menC and having a genetic alteration that increases expression of a protein encoded by cyoB; 
 (f) attenuation of the proteins encoded by sucCD, yciA, cydA or cydB and menC and having a genetic alteration that increases expression of an protein encoded by cyoB; 
 (g) attenuation of the proteins encoded by sucCD and cydA or cydB; 
 (h) attenuation of the proteins encoded by sucCD and cydA or cydB and pykF; 
 (i) attenuation of the proteins encoded by sucCD and cydA or cydB, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (j) attenuation of the proteins encoded by sucCD and cydA or cydB and pykF, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (k) attenuation of the proteins encoded by sucCD, yciA and cydA or cydB; 
 (l) attenuation of the proteins encoded by sucCD, yciA and cydA or cydB and pykF; 
 (m) attenuation of the proteins encoded by sucCD, yciA and cydA or cydB, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (n) attenuation of the proteins encoded by sucCD, yciA and cydA or cydB and pykF, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (o) attenuation of the proteins encoded by sucCD, yciA, and cydA or cydB and menC; 
 (p) attenuation of the proteins encoded by sucCD, yciA and cydA or cydB and menC, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (q) attenuation of the proteins encoded by sucCD and pykF, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (r) attenuation of the protein encoded by clpA; 
 (s) attenuation of the protein encoded by menC; 
 (t) attenuation of the protein encoded by menC and cydA or cydB; 
 (u) attenuation of the protein encoded by pykF and/or pykA; 
 (v) having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (w) attenuation of cydA or cydB and sucCD, arcA and crr, and having a genetic alteration that increases expression of a protein encoded by ackA and pta; 
 (x) attenuation of cydA or cydB and arcA; 
 (y) attenuation of cydA or cydB, and having a genetic alteration that increases expression of a protein encoded by pntAB; 
 (z) attenuation of cydA or cydB and pykF; and 
 (aa) attenuation of cydA or cydB and pykF, and having a genetic alteration that increases expression of a protein encoded by pntAB. 
   
     
     
         2 .- 7 . (canceled) 
     
     
         8 . A method of producing a bioderived compound comprising culturing a non-naturally occurring microbial organism of  claim 1  for a sufficient period of time under conditions sufficient to produce said bioderived compound. 
     
     
         9 . A bioderived compound produced by the non-naturally occurring microbial organism of  claim 1 . 
     
     
         10 . A non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate. 
     
     
         11 .- 40 . (canceled) 
     
     
         41 . A non-naturally occurring microbial organism comprising a gene disruption of a gene encoding YciA CoA hydrolase and a metabolically engineered pathway for producing a bioderived compound from a TCA cycle intermediate. 
     
     
         42 .- 70 . (canceled) 
     
     
         71 . A non-naturally occurring microbial organism of  claim 10 , wherein said microbial organism is selected from the group consisting of bacteria, yeast, fungus or other microorganism applicable to a fermentation process. 
     
     
         72 .- 73 . (canceled) 
     
     
         74 . A method of producing a bioderived compound comprising culturing a non-naturally occurring microbial organism of  claim 10  for a sufficient period of time under conditions sufficient to produce said bioderived compound. 
     
     
         75 . A bioderived compound produced by the non-naturally occurring microbial organism of  claim 10 .