A non-naturally occurring microbial organism includes a microbial organism having a reductive TCA or Wood-Ljungdahl pathway in which at least one exogenous nucleic acid encoding these pathway enzymes is expressed in a sufficient amount to enhance carbon flux through acetyl-CoA. A method for enhancin
A non-naturally occurring microbial organism includes a microbial organism having a reductive TCA or Wood-Ljungdahl pathway in which at least one exogenous nucleic acid encoding these pathway enzymes is expressed in a sufficient amount to enhance carbon flux through acetyl-CoA. A method for enhancing carbon flux through acetyl-CoA includes culturing theses non-naturally occurring microbial organisms under conditions and for a sufficient period of time to produce a product having acetyl-CoA as a building block. Another non-naturally occurring microbial organism includes at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance the availability of reducing equivalents in the presence of carbon monoxide or hydrogen, thereby increasing the yield of redox-limited products via carbohydrate-based carbon feedstock. A method for enhancing the availability of reducing equivalents in the presence of carbon monoxide or hydrogen includes culturing this organism for a sufficient period of time to produce a product.
대표청구항▼
1. A non-naturally occurring microbial organism comprising: (1) at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said at least one exogenous nucleic acid encodes an enzyme selected from the group consisting of:
1. A non-naturally occurring microbial organism comprising: (1) at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said at least one exogenous nucleic acid encodes an enzyme selected from the group consisting of: i) an Acetyl-CoA synthase,ii) a Pyruvate ferredoxin oxidoreductase or pyruvate dehydrogenase, andiii) a pyruvate formate lyase;(2) (a) an isopropanol pathway that converts acetyl-CoA to isopropanol, wherein the isopropanol pathway comprises 1) an acetoacetyl-CoA thiolase; 2) an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase/acetoacetate kinase; 3) an acetoacetate decarboxylase; and 4) an isopropanol dehydrogenase; (b) a 1,4-butanediol pathway that converts acetyl-CoA to 1,4-butanediol; wherein the 1,4-butanediol pathway comprises at least five enzymes selected from the group consisting of: 1) an acetoacetyl-CoA thiolase; 2) a 3-hydroxybutyryl-CoA dehydrogenase; 3) a crotonase; 4) a crotonyl-CoA hydratase; 5) a 4-hydroxybutyryl-CoA reductase (alcohol forming); 6) a 4-hydroxybutyryl-CoA reductase (aldehyde forming); 7) a 1,4-butanediol dehydrogenase; 8) a 4-hydroxybutyryl-CoA transferase, 4-hydroxybutyryl-CoA synthetase, 4-hydroxybutyryl-CoA hydrolase, or phosphotrans-4-hydroxybutyrylase/4-Hydroxybutyrate kinase; and 9) a 4-hydroxybutyrate reductase; or(c) a 4-hydroxybutyrate pathway that converts acetyl-CoA to 4-hydroxybutyrate, wherein said 4-hydroxybutyrate pathway comprises at least five enzymes selected from the group consisting of: 1) an acetoacetyl-CoA thiolase; 2) a 3-hydroxybutyryl-CoA dehydrogenase; 3) a crotonase; 4) a crotonyl-CoA hydratase; 5) a 4-hydroxybutyryl-CoA transferase, hydrolase or synthetase; 6) a phosphotrans-4-hydroxybutyrylase; and 7) a 4-hydroxybutyrate kinase; and(3) a reductive TCA (rTCA) pathway, wherein said microbial organism comprises at least one exogenous nucleic acid encoding a rTCA pathway enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said rTCA enzyme is selected from the group consisting of 1) an ATP-citrate lyase, 2) a citrate lyase, 3) a fumarate reductase, and 4) an alpha-ketoglutarate:ferredoxin oxidoreductase. 2. The organism of claim 1, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, an acetate kinase, a phosphotransacetylase, an NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 3. The organism of claim 1, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of a carbon monoxide dehydrogenase, a hydrogenase, a NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 4. The organism of claim 3, wherein said microbial organism utilizes a carbon feedstock selected from (i) CO, CO2, and H2, (ii) synthesis gas comprising CO and and (iii) synthesis gas comprising CO, CO2, and H2. 5. The non-naturally occurring microbial organism of claim 1, wherein said organism comprises: (1) said at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said at least one exogenous nucleic acid encodes an enzyme selected from the group consisting of i) an Acetyl-CoA synthase, ii) a Pyruvate ferredoxin oxidoreductase or pyruvate dehydrogenase, and iii) a pyruvate formate lyase;(2) said isopropanol pathway that converts acetyl-CoA to isopropanol, wherein the isopropanol pathway comprises 1) an acetoacetyl-CoA thiolase;2) an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase / acetoacetate kinase;3) an acetoacetate decarboxylase; and4) an isopropanol dehydrogenase; and(3) said rTCA pathway, wherein said microbial organism comprises at least one exogenous nucleic acid encoding a rTCA pathway enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said rTCA enzyme is selected from the group consisting of 1) an ATP-citrate lyase,2) a citrate lyase,3) a fumarate reductase, and4) an alpha-ketoglutarate:ferredoxin oxidoreductase. 6. The organism of claim 5, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, an acetate kinase, a phosphotransacetylase, an NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 7. The organism of claim 5, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of a carbon monoxide dehydrogenase, a hydrogenase, a NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 8. The organism of claim 7, wherein said microbial organism utilizes a carbon feedstock selected from (i) CO, CO2, and H2, (ii) synthesis gas comprising CO and H2, and (iii) synthesis gas comprising CO, CO2, and H2. 9. The organism of claim 5, wherein at least one of the isopropanol pathway enzymes is encoded by an exogenous nucleic acid. 10. The non-naturally occurring microbial organism of claim 1, wherein said organism comprises: (1) said at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said at least one exogenous nucleic acid encodes an enzyme selected from the group consisting of: i) an Acetyl-CoA synthase, ii) a Pyruvate ferredoxin oxidoreductase or pyruvate dehydrogenase, and iii) a pyruvate formate lyase;(2) said 1,4-butanediol pathway that converts acetyl-CoA to 1,4-butanediol; wherein the 1,4-butanediol pathway comprises at least five enzymes selected from the group consisting of: 1) an acetoacetyl-CoA thiolase;2) a 3-hydroxybutyryl-CoA dehydrogenase;3) a crotonase;4) a crotonyl-CoA hydratase;5) a 4-hydroxybutyryl-CoA reductase (alcohol forming);6) a 4-hydroxybutyryl-CoA reductase (aldehyde forming);7) a 1,4-butanediol dehydrogenase;8) a 4-hydroxybutyryl-CoA transferase, 4-hydroxybutyryl-CoA synthetase, 4-hydroxybutyryl-CoA hydrolase, or phosphotrans -4-hydroxybutyrylase / 4-Hydroxybutyrate kinase; and9) a 4-hydroxybutyrate reductase; and(3) said rTCA pathway, wherein said microbial organism comprises at least one exogenous nucleic acid encoding a rTCA pathway enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said rTCA enzyme is selected from the group consisting of 1) an ATP-citrate lyase,2) a citrate lyase,3) a fumarate reductase, and4) an alpha-ketoglutarate:ferredoxin oxidoreductase. 11. The organism of claim 10, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, an acetate kinase, a phosphotransacetylase, an NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 12. The organism of claim 10, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of a carbon monoxide dehydrogenase, a hydrogenase, a NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 13. The organism of claim 12, wherein said microbial organism utilizes a carbon feedstock selected from (i) CO, CO2, and H2, (ii) synthesis gas comprising CO and H2, and (iii) synthesis gas comprising CO, CO2, and H2. 14. The organism of claim 10, wherein at least one of the 1,4-butanediol enzymes is encoded by an exogenous nucleic acid. 15. The non-naturally occurring microbial organism of claim 1, wherein said organism comprises: (1) said at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said at least one exogenous nucleic acid encodes an enzyme selected from the group consisting of: i) an Acetyl-CoA synthase, ii) a Pyruvate ferredoxin oxidoreductase or pyruvate dehydrogenase, and iii) a pyruvate formate lyase;(2) said 4-hydroxybutyrate pathway that converts acetyl-CoA to 4-hydroxybutyrate, wherein said 4-hydroxybutyrate pathway comprises at least five enzymes selected from the group consisting of: 1) an acetoacetyl-CoA thiolase;2) a 3-hydroxybutyryl-CoA dehydrogenase;3) a crotonase;4) a crotonyl-CoA hydratase;5) a 4-hydroxybutyryl-CoA transferase, hydrolase or synthetase;6) a phosphotrans-4-hydroxybutyrylase; and7) a 4-hydroxybutyrate kinase; and(3) said rTCA pathway, wherein said microbial organism comprises at least one exogenous nucleic acid encoding a rTCA pathway enzyme expressed in a sufficient amount to enhance carbon flux through acetyl-CoA, wherein said rTCA enzyme is selected from the group consisting of 1) an ATP-citrate lyase,2) a citrate lyase,3) a fumarate reductase, and4) an alpha-ketoglutarate:ferredoxin oxidoreductase. 16. The organism of claim 15, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, an acetate kinase, a phosphotransacetylase, an NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 17. The organism of claim 15, further comprising an exogenous nucleic acid encoding an enzyme selected from the group consisting of a carbon monoxide dehydrogenase, a hydrogenase, a NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 18. The organism of claim 17, wherein said microbial organism utilizes a carbon feedstock selected from (i) CO, CO2, and H2, (ii) synthesis gas comprising CO and H2, and (iii) synthesis gas comprising CO, CO2, and H2. 19. The organism of claim 15, wherein the at least one of the 4-hydroxybutyrate pathway enzymes is encoded by an exogenous nucleic acid.
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