Microorganisms for producing butadiene and methods related thereto

Abstract

The invention provides non-naturally occurring microbial organisms having a butadiene or crotyl alcohol pathway. The invention additionally provides methods of using such organisms to produce butadiene or crotyl alcohol.

1 . A non-naturally occurring microbial organism, comprising a microbial organism having a butadiene pathway comprising at least one exogenous nucleic acid encoding a butadiene pathway enzyme expressed in a sufficient amount to produce butadiene; said non-naturally occurring microbial organism further comprising:
 (a) a reductive TCA pathway comprising at least one exogenous nucleic acid encoding a reductive TCA pathway enzyme, wherein said at least one exogenous nucleic acid is selected from an ATP-citrate lyase, a citrate lyase, a citryl-CoA synthetase, a citryl-CoAlyase, a fumarate reductase, and an alpha-ketoglutarate:ferredoxin oxidoreductase;   (b) a reductive TCA pathway comprising at least one exogenous nucleic acid encoding a reductive TCA pathway enzyme, wherein said at least one exogenous nucleic acid is selected from a pyruvate:ferredoxin oxidoreductase, a phosphoenolpyruvate carboxylase, a phosphoenolpyruvate carboxykinase, a CO dehydrogenase, and an H 2  hydrogenase; or   (c) at least one exogenous nucleic acid encodes an enzyme selected from a CO dehydrogenase, an H 2  hydrogenase, and combinations thereof,   wherein said butadiene pathway comprises a pathway selected from:   (i) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (ii) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (iii) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (iv) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase and a crotonate reductase;   (v) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (vi) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase and a crotyl alcohol diphosphokinase.   (vii) a glutaconyl-CoA decarboxylase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase.   (viii) a glutaconyl-CoA decarboxylase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (ix) a glutaconyl-CoA decarboxylase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (x) a glutaconyl-CoA decarboxylase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase, or transferase and a crotonate reductase;   (xi) a glutaconyl-CoA decarboxylase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xii) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene a glutaconyl-CoA decarboxylase and a crotyl alcohol diphosphokinase;   (xiii) a glutaryl-CoA dehydrogenase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (xiv) a glutaryl-CoA dehydrogenase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (xv) a glutaryl-CoA dehydrogenase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (xvi) a glutaryl-CoA dehydrogenase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase, or transferase and a crotonate reductase;   (xvii) a glutaryl-CoA dehydrogenase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xviii) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a glutaryl-CoA dehydrogenase and a crotyl alcohol diphosphokinase;   (xix) an 3-aminobutyryl-CoA deaminase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (xx) an 3-aminobutyryl-CoA deaminase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (xxi) an 3-aminobutyryl-CoA deaminase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (xxii) an 3-aminobutyryl-CoA deaminase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase and a crotonate reductase;   (xxiii) an 3-aminobutyryl-CoA deaminase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xxiv) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a 3-aminobutyryl-CoA deaminase and a crotyl alcohol diphosphokinase;   (xxv) a 4-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (xxvi) a 4-hydroxybutyryl-CoA dehydratase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (xxvii) a 4-hydroxybutyryl-CoA dehydratase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (xxviii) a 4-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase and a crotonate reductase;   (xxix) a 4-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xxx) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a 4-hydroxybutyryl-CoA dehydratase and a crotyl alcohol diphosphokinase;   (xxxi) an erythrose-4-phosphate reductase, an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase and a butadiene synthase;   (xxxii) an erythrose-4-phosphate reductase, an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase, a butenyl 4-diphosphate isomerase and a butadiene synthase;   (xxxiii) an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase, a butadiene synthase, an erythrose-4-phosphate kinase, an erythrose reductase and a erythritol kinase;   (xxxiv) an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase, a butenyl 4-diphosphate isomerase, a butadiene synthase, an erythrose-4-phosphate kinase, an erythrose reductase and an erythritol kinase;   (xxxv) a malonyl-CoA:acetyl-CoA acyltransferase, an 3-oxoglutaryl-CoA reductase (ketone-reducing), a 3-hydroxyglutaryl-CoA reductase (aldehyde forming), a 3-hydroxy-5-oxopentanoate reductase, a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase and a butadiene synthase;   (xxxvi) a malonyl-CoA:acetyl-CoA acyltransferase, a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase, an 3-oxoglutaryl-CoA reductase (aldehyde forming), a 3,5-dioxopentanoate reductase (aldehyde reducing) and a 5-hydroxy-3-oxopentanoate reductase;   (xxxvii) a malonyl-CoA:acetyl-CoA acyltransferase, a 3-hydroxy-5-oxopentanoate reductase, a 3,5-dihydroxypentanoate kinase, a 3-Hydroxy-5-phosphonatooxypentanoate kinase, a 3-Hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase, an 3-oxoglutaryl-CoA reductase (aldehyde forming) and a 3,5-dioxopentanoate reductase (ketone reducing);   (xxxviii) a malonyl-CoA:acetyl-CoA acyltransferase, a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase, a 5-hydroxy-3-oxopentanoate reductase and a 3-oxo-glutaryl-CoA reductase (CoA reducing and alcohol forming); and   (xxxix) a butadiene pathway comprising a malonyl-CoA:acetyl-CoA acyltransferase, an 3-oxoglutaryl-CoA reductase (ketone-reducing), a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase and a 3-hydroxyglutaryl-CoA reductase (alcohol forming).   
     
     
         2 . The non-naturally occurring microbial organism of  claim 1 , wherein said microbial organism comprising (a) further comprises an exogenous nucleic acid encoding an enzyme selected from a pyruvate:ferredoxin oxidoreductase, an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, an acetate kinase, a phosphotransacetylase, an acetyl-CoA synthetase, an NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 
     
     
         3 . The non-naturally occurring microbial organism of  claim 1 , wherein said microbial organism comprising (b) further comprises an exogenous nucleic acid encoding an enzyme selected from an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, and combinations thereof. 
     
     
         4 . The non-naturally occurring microbial organism of  claim 1 , wherein said microbial organism comprises two, three, four, five, six or seven exogenous nucleic acids each encoding a butadiene pathway enzyme. 
     
     
         5 . The non-naturally occurring microbial organism of  claim 4 , wherein said microbial organism comprises exogenous nucleic acids encoding each of the enzymes selected from:
 (i) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (ii) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (iii) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (iv) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase and a crotonate reductase;   (v) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (vi) an acetyl-CoA:acetyl-CoA acyltransferase, an acetoacetyl-CoA reductase, a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase and a crotyl alcohol diphosphokinase.   (vii) a glutaconyl-CoA decarboxylase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase.   (viii) a glutaconyl-CoA decarboxylase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (ix) a glutaconyl-CoA decarboxylase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (x) a glutaconyl-CoA decarboxylase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase, or transferase and a crotonate reductase;   (xi) a glutaconyl-CoA decarboxylase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xii) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene a glutaconyl-CoA decarboxylase and a crotyl alcohol diphosphokinase;   (xiii) a glutaryl-CoA dehydrogenase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (xiv) a glutaryl-CoA dehydrogenase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (xv) a glutaryl-CoA dehydrogenase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (xvi) a glutaryl-CoA dehydrogenase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase, or transferase and a crotonate reductase;   (xvii) a glutaryl-CoA dehydrogenase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xviii) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a glutaryl-CoA dehydrogenase and a crotyl alcohol diphosphokinase;   (xix) an 3-aminobutyryl-CoA deaminase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (xx) an 3-aminobutyryl-CoA deaminase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (xxi) an 3-aminobutyryl-CoA deaminase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (xxii) an 3-aminobutyryl-CoA deaminase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase and a crotonate reductase;   (xxiii) an 3-aminobutyryl-CoA deaminase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xxiv) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a 3-aminobutyryl-CoA deaminase and a crotyl alcohol diphosphokinase;   (xxv) a 4-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase and a butadiene synthase;   (xxvi) a 4-hydroxybutyryl-CoA dehydratase, a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase and crotonyl-CoA reductase (alcohol forming);   (xxvii) a 4-hydroxybutyryl-CoA dehydratase, a butadiene synthase, a crotonyl-CoA reductase (alcohol forming) and a crotyl alcohol diphosphokinase;   (xxviii) a 4-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a crotyl alcohol kinase, a 2-butenyl-4-phosphate kinase, a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase and a crotonate reductase;   (xxix) a 4-hydroxybutyryl-CoA dehydratase, a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a crotonyl-CoA hydrolase, synthetase or transferase, a crotonate reductase and a crotyl alcohol diphosphokinase;   (xxx) a 3-hydroxybutyryl-CoA dehydratase, a crotonyl-CoA reductase (aldehyde forming), a crotonaldehyde reductase (alcohol forming), a butadiene synthase, a 4-hydroxybutyryl-CoA dehydratase and a crotyl alcohol diphosphokinase;   (xxxi) an erythrose-4-phosphate reductase, an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase and a butadiene synthase;   (xxxii) an erythrose-4-phosphate reductase, an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase, a butenyl 4-diphosphate isomerase and a butadiene synthase;   (xxxiii) an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase, a butadiene synthase, an erythrose-4-phosphate kinase, an erythrose reductase and a erythritol kinase;   (xxxiv) an erythritol-4-phospate cytidylyltransferase, a 4-(cytidine 5′-diphospho)-erythritol kinase, an erythritol 2,4-cyclodiphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate synthase, a 1-hydroxy-2-butenyl 4-diphosphate reductase, a butenyl 4-diphosphate isomerase, a butadiene synthase, an erythrose-4-phosphate kinase, an erythrose reductase and an erythritol kinase;   (xxxv) a malonyl-CoA:acetyl-CoA acyltransferase, an 3-oxoglutaryl-CoA reductase (ketone-reducing), a 3-hydroxyglutaryl-CoA reductase (aldehyde forming), a 3-hydroxy-5-oxopentanoate reductase, a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase and a butadiene synthase;   (xxxvi) a malonyl-CoA:acetyl-CoA acyltransferase, a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase, an 3-oxoglutaryl-CoA reductase (aldehyde forming), a 3,5-dioxopentanoate reductase (aldehyde reducing) and a 5-hydroxy-3-oxopentanoate reductase;   (xxxvii) a malonyl-CoA:acetyl-CoA acyltransferase, a 3-hydroxy-5-oxopentanoate reductase, a 3,5-dihydroxypentanoate kinase, a 3-Hydroxy-5-phosphonatooxypentanoate kinase, a 3-Hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase, an 3-oxoglutaryl-CoA reductase (aldehyde forming) and a 3,5-dioxopentanoate reductase (ketone reducing);   (xxxviii) a malonyl-CoA:acetyl-CoA acyltransferase, a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase, a 5-hydroxy-3-oxopentanoate reductase and a 3-oxo-glutaryl-CoA reductase (CoA reducing and alcohol forming); and   (xxxix) a butadiene pathway comprising a malonyl-CoA:acetyl-CoA acyltransferase, an 3-oxoglutaryl-CoA reductase (ketone-reducing), a 3,5-dihydroxypentanoate kinase, a 3-hydroxy-5-phosphonatooxypentanoate kinase, a 3-hydroxy-5-[hydroxy(phosphonooxy)phosphoryl]oxy pentanoate decarboxylase, a butenyl 4-diphosphate isomerase, a butadiene synthase and a 3-hydroxyglutaryl-CoA reductase (alcohol forming).   
     
     
         6 . The non-naturally occurring microbial organism of  claim 1 , wherein said microbial organism comprises two, three, four or five exogenous nucleic acids each encoding enzymes of (a), (b) or (c). 
     
     
         7 . The non-naturally occurring microbial organism of  claim 6 , wherein said microbial organism comprising (a) comprises three exogenous nucleic acids encoding ATP-citrate lyase or citrate lyase, a fumarate reductase, and an alpha-ketoglutarate:ferredoxin oxidoreductase;
 wherein said microbial organism comprising (b) comprises four exogenous nucleic acids encoding a pyruvate:ferredoxin oxidoreductase, a phosphoenolpyruvate carboxylase or a phosphoenolpyruvate carboxykinase, a CO dehydrogenase, and an H2 hydrogenase; or   wherein said microbial organism comprising (c) comprises two exogenous nucleic acids encoding CO dehydrogenase and H2 hydrogenase.   
     
     
         8 . The non-naturally occurring microbial organism of  claim 1 , wherein said at least one exogenous nucleic acid is a heterologous nucleic acid. 
     
     
         9 . The non-naturally occurring microbial organism of  claim 1 , wherein said non-naturally occurring microbial organism is in a substantially anaerobic culture medium. 
     
     
         10 . A method for producing butadiene, comprising culturing the non-naturally occurring microbial organism of  claim 1  under conditions and for a sufficient period of time to produce butadiene. 
     
     
         11 . A non-naturally occurring microbial organism, comprising a microbial organism having a crotyl alcohol pathway comprising at least one exogenous nucleic acid encoding a crotyl alcohol pathway enzyme expressed in a sufficient amount to produce crotyl alcohol; said non-naturally occurring microbial organism further comprising:
 (a) a reductive TCA pathway comprising at least one exogenous nucleic acid encoding a reductive TCA pathway enzyme, wherein said at least one exogenous nucleic acid is selected from an ATP-citrate lyase, a citrate lyase, a citryl-CoA synthetase, a citryl-CoA lyase, a fumarate reductase, and an alpha-ketoglutarate:ferredoxin oxidoreductase;   (b) a reductive TCA pathway comprising at least one exogenous nucleic acid encoding a reductive TCA pathway enzyme, wherein said at least one exogenous nucleic acid is selected from a pyruvate:ferredoxin oxidoreductase, a phosphoenolpyruvate carboxylase, a phosphoenolpyruvate carboxykinase, a CO dehydrogenase, and an H 2  hydrogenase; or   (c) at least one exogenous nucleic acid encodes an enzyme selected from a CO dehydrogenase, an H 2  hydrogenase, and combinations thereof;   wherein said crotyl alcohol pathway comprises a pathway selected from:   (i) an acetyl-CoA:acetyl-CoA acyltransferase; an acetoacetyl-CoA reductase; a 3-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (ii) an acetyl-CoA:acetyl-CoA acyltransferase; an acetoacetyl-CoA reductase; a 3-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming);   (iii) an acetyl-CoA:acetyl-CoA acyltransferase; an acetoacetyl-CoA reductase; a 3-hydroxybutyryl-CoA dehydratase; and a crotonyl-CoA reductase (alcohol forming);   (iv) a glutaconyl-CoA decarboxylase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (v) a glutaconyl-CoA decarboxylase; a crotonyl-CoA reductase (aldehyde forming); and   a crotonaldehyde reductase (alcohol forming); and   (vi) a glutaconyl-CoA decarboxylase; and a crotonyl-CoA reductase (alcohol forming).   (vii) a glutaryl-CoA dehydrogenase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (viii) a glutaryl-CoA dehydrogenase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming);   (ix) a glutaryl-CoA dehydrogenase; and a crotonyl-CoA reductase (alcohol forming).   (x) a 3-aminobutyryl-CoA deaminase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (xi) a 3-aminobutyryl-CoA deaminase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming);   (xii) a 3-aminobutyryl-CoA deaminase; and a crotonyl-CoA reductase (alcohol forming).   (xiii) a 4-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (xiv) a 4-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming); and   (xv) a 4-hydroxybutyryl-CoA dehydratase; and a crotonyl-CoA reductase (alcohol forming).   
     
     
         12 . The non-naturally occurring microbial organism of  claim 11 , wherein said microbial organism comprising (a) further comprises an exogenous nucleic acid encoding an enzyme selected from a pyruvate:ferredoxin oxidoreductase, an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, an acetate kinase, a phosphotransacetylase, an acetyl-CoA synthetase, an NAD(P)H:ferredoxin oxidoreductase, ferredoxin, and combinations thereof. 
     
     
         13 . The non-naturally occurring microbial organism of  claim 11 , wherein said microbial organism comprising (b) further comprises an exogenous nucleic acid encoding an enzyme selected from an aconitase, an isocitrate dehydrogenase, a succinyl-CoA synthetase, a succinyl-CoA transferase, a fumarase, a malate dehydrogenase, and combinations thereof. 
     
     
         14 . The non-naturally occurring microbial organism of  claim 11 , wherein said microbial organism comprises two, three, four, five, six or seven exogenous nucleic acids each encoding a crotyl alcohol pathway enzyme. 
     
     
         15 . The non-naturally occurring microbial organism of  claim 14 , wherein said microbial organism comprises exogenous nucleic acids encoding each of the enzymes selected from:
 (i) an acetyl-CoA:acetyl-CoA acyltransferase; an acetoacetyl-CoA reductase; a 3-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (ii) an acetyl-CoA:acetyl-CoA acyltransferase; an acetoacetyl-CoA reductase; a 3-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming);   (iii) an acetyl-CoA:acetyl-CoA acyltransferase; an acetoacetyl-CoA reductase; a 3-hydroxybutyryl-CoA dehydratase; and a crotonyl-CoA reductase (alcohol forming);   (iv) a glutaconyl-CoA decarboxylase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (v) a glutaconyl-CoA decarboxylase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming); and   (vi) a glutaconyl-CoA decarboxylase; and a crotonyl-CoA reductase (alcohol forming).   (vii) a glutaryl-CoA dehydrogenase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (viii) a glutaryl-CoA dehydrogenase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming);   (ix) a glutaryl-CoA dehydrogenase; and a crotonyl-CoA reductase (alcohol forming).   (x) a 3-aminobutyryl-CoA deaminase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (xi) a 3-aminobutyryl-CoA deaminase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming);   (xii) a 3-aminobutyryl-CoA deaminase; and a crotonyl-CoA reductase (alcohol forming).   (xiii) a 4-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA hydrolase, synthase, or transferase; a crotonate reductase; and a crotonaldehyde reductase (alcohol forming);   (xiv) a 4-hydroxybutyryl-CoA dehydratase; a crotonyl-CoA reductase (aldehyde forming); and a crotonaldehyde reductase (alcohol forming); and   (xv) a 4-hydroxybutyryl-CoA dehydratase; and a crotonyl-CoA reductase (alcohol forming).   
     
     
         16 . The non-naturally occurring microbial organism of  claim 11 , wherein said microbial organism comprises two, three, four or five exogenous nucleic acids each encoding enzymes of (a), (b) or (c). 
     
     
         17 . The non-naturally occurring microbial organism of  claim 16 , wherein said microbial organism comprising (a) comprises three exogenous nucleic acids encoding ATP-citrate lyase or citrate lyase, a fumarate reductase, and an alpha-ketoglutarate:ferredoxin oxidoreductase;
 wherein said microbial organism comprising (b) comprises four exogenous nucleic acids encoding a pyruvate:ferredoxin oxidoreductase, a phosphoenolpyruvate carboxylase or a phosphoenolpyruvate carboxykinase, a CO dehydrogenase, and an H 2  hydrogenase; or   wherein said microbial organism comprising (c) comprises two exogenous nucleic acids encoding a CO dehydrogenase and an H2 hydrogenase.   
     
     
         18 . The non-naturally occurring microbial organism of  claim 11 , wherein said at least one exogenous nucleic acid is a heterologous nucleic acid. 
     
     
         19 . The non-naturally occurring microbial organism of  claim 11 , wherein said non-naturally occurring microbial organism is in a substantially anaerobic culture medium. 
     
     
         20 . A method for producing crotyl alcohol, comprising culturing the non-naturally occurring microbial organism of  claim 11  under conditions and for a sufficient period of time to produce crotyl alcohol.