Eukaryotic organisms and methods for increasing the availability of cytosolic acetyl-coa, and for producing 1,3-butanediol

A non-naturally occurring microbial organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and:

• (1) wherein the organism:
• i. has lower or no enzymatic activity that converts acetoacetyl-CoA to acetoacetate as compared to a wild-type version of the organism;
• ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts acetoacetyl-CoA to acetoacetate;
• iii. expresses an attenuated acetoacetyl-CoA hydrolase or transferase;
• or
• iv. comprises a disruption in an endogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase;
• (2) wherein the organism:
• i. has lower or no enzymatic activity that converts 3-hydroxybutyryl-CoA to 3-hydroxybutyrate as compared to a wild-type version of the organism;
• ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts 3-hydroxybutyryl-CoA to 3-hydroxybutyrate;
• iii. expresses an attenuated 3-hydroxybutyryl-CoA hydrolase or transferase;
• or
• iv. comprises a disruption in an endogenous nucleic acid encoding a 3-hydroxybutyryl-CoA hydrolase or transferase;
• (3) wherein the organism:
• i. has lower or no enzymatic activity that converts 3-hydroxybutyraldehyde to 3-hydroxybutyrate as compared to a wild-type version of the organism;
• ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts 3-hydroxybutyraldehyde to 3-hydroxybutyrate;
• iii. expresses an attenuated 3-hydroxybutyraldehyde dehydrogenase;
• or
• iv. comprises a disruption in an endogenous nucleic acid encoding a 3-hydroxybutyraldehyde dehydrogenase;
• (4) wherein the organism:
• i. has lower or no enzymatic activity that catalyzes 1,3-butanediol to 3-oxobutanol as compared to a wild-type version of the organism;
• ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that catalyzes 1,3-butanediol to 3-oxobutanol;
• iii. expresses an attenuated 1,3-butanediol dehydrogenase;
• or
• iv. comprises a disruption in an endogenous nucleic acid encoding a 1,3-butanediol dehydrogenase;
• (5) wherein the organism:
• i. has lower or no enzymatic activity that converts G3P to glycerol as compared to a wild-type version of the organism;
• ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts G3P to glycerol;
• iii. expresses an attenuated G3P dehydrogenase or G3P phosphatase;
• or
• iv. comprises a disruption in an endogenous nucleic acid encoding a G3P dehydrogenase or a G3P phosphatase;
• (6) wherein the organism:
• i. has lower or no enzymatic activity that converts pyruvate to acetaldehyde as compared to a wild-type version of the organism;
• ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts pyruvate to acetaldehyde;
• iii. expresses an attenuated pyruvate decarboxylase;
• or
• iv. comprises a disruption in an endogenous nucleic acid encoding a pyruvate decarboxylase;
• or
• (7) wherein the organism:
• i. has lower or no enzymatic activity that converts acetyl-CoA to ethanol as compared to a wild-type version of the organism;
• ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts acetyl-CoA to ethanol;
• iii. expresses an attenuated ethanol dehydrogenase or acetaldehyde dehydrogenase;
• or
• iv. comprises a disruption in an endogenous nucleic acid encoding an ethanol dehydrogenase or acetaldehyde dehydrogenase.