METHODS AND ORGANISMS WITH INCREASED CARBON FLUX EFFICIENCIES
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 .