MICROORGANISMS AND METHODS FOR THE BIOSYNTHESIS OF ADIPATE, HEXAMETHYLENEDIAMINE AND 6-AMINOCAPROIC ACID

• US 20190330670A1
• Filed: 12/07/2018
• Published: 10/31/2019
• Est. Priority Date: 05/07/2009
• Status: Active Grant

• Current Assignee: Genomatica Incorporated
• Original Assignee: Genomatica Incorporated
• Inventors: Burk, Mark J., Burgard, Anthony P., Osterhout, Robin E., Pharkya, Priti
• Granted Patent: US 11,208,673 B2
• Time in Patent Office: Days
• CPC Class Codes: C12N 1/38 Chemical stimulation of growth or activity by addition of chemical compounds which are not essential growth factors; Stimulation of growth by removal of a chemical compound C12N1/34 takes precedence
• CPC Class Codes: C12N 15/52 Genes encoding for enzymes or proenzymes
• CPC Class Codes: C12N 9/1029 transferring groups other than amino-acyl groups (2.3.1)
• CPC Class Codes: C12N 9/1096 transferring nitrogenous groups (2.6)
• CPC Class Codes: C12N 9/88 Lyases (4.)
• CPC Class Codes: C12P 13/001 Amines; Imines
• CPC Class Codes: C12P 13/005 Amino acids other than alpha- or beta amino acids, e.g. gamma amino acids
• CPC Class Codes: C12P 13/02 Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes peptides C12P21/00 or C07K
• CPC Class Codes: C12P 17/10 Nitrogen as only ring hetero atom
• CPC Class Codes: C12P 17/12 containing a six-membered hetero ring
• CPC Class Codes: C12P 7/40 containing a carboxyl group including Peroxycarboxylic acids
• CPC Class Codes: C12P 7/44 Polycarboxylic acids
• CPC Class Codes: C12Y 103/01 with NAD+ or NADP+ as acceptor (1.3.1)
• CPC Class Codes: C12Y 301/02 Thioester hydrolases (3.1.2)
• CPC Class Codes: C12Y 402/01 Hydro-lyases (4.2.1)

Abstract

The invention provides a non-naturally occurring microbial organism having a 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in the respective 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The invention additionally provides a method for producing 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid. The method can include culturing a 6-aminocaproic acid, caprolactam or hexametheylenediamine producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway enzyme in a sufficient amount to produce the respective product, under conditions and for a sufficient period of time to produce 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid.

Claims

1-94. -94. (canceled)

95. A non-naturally occurring microbial organism, comprising a microbial organism having a 6-aminocaproic acid (6-ACA) pathway comprising at least one exogenous nucleic acid encoding a 6-ACA pathway enzyme expressed in a sufficient amount to produce 6-ACA, said 6-ACA pathway comprising a 4-hydroxy-2-oxoheptane-1,7-dioate (HODH) aldolase, a 2-oxohept-4-ene-1,7-dioate (OHED) hydratase, a 2-oxohept-4-ene-1,7-dioate (OHED) reductase, a 2-oxoheptane-1,7-dioate (2-OHD) decarboxylase, an adipate semialdehyde aminotransferase, an adipate semialdehyde oxidoreductase (aminating), a 2-oxohept-4-ene-1,7-dioate (OHED) decarboxylase, a 6-oxohex-4-enoate (6-OHE) reductase, a 2-oxoheptane-1,7-dioate (2-OHD) aminotransferase, a 2-oxoheptane-1,7-dioate (2-OHD) oxidoreductase (aminating), a 2-aminoheptane-1,7-dioate (2-AHD) decarboxylase, a 2-oxohept-4-ene-1,7-dioate (OHED) aminotransferase, a 2-oxohept-4-ene-1,7-dioate (OHED) oxidoreductase (aminating), a 2-aminohept-4-ene-1,7-dioate (2-AHE) reductase, a 4-hydroxy-2-oxoheptane-1,7-dioate (HODH) formate-lyase, a 4-hydroxy-2-oxoheptane-1,7-dioate (HODH) dehydrogenase, a 3-hydroxyadipyl-CoA dehydratase, a 2,3-dehydroadipyl-CoA reductase, a adipyl-CoA dehydrogenase, a 2-oxohept-4-ene-1,7-dioate (OHED) formate-lyase, a 2-oxohept-4-ene-1,7-dioate (OHED) dehydrogenase, a 2-oxoheptane-1,7-dioate (2-OHD) formate-lyase, a 2-oxoheptane-1,7-dioate (2-OHD) dehydrogenase, or a pyruvate formate-lyase activating enzyme.

96. The non-naturally occurring microbial organism of claim 95, wherein said microbial organism comprises at least one exogenous nucleic acid each encoding a 6-ACA pathway enzyme, said 6-ACA pathway comprising a pathway selected from the group consisting of:

(i) an HODH aldolase;

an OHED hydratase;

an OHED reductase;

a 2-OHD decarboxylase;

or an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating);

(ii) an HODH aldolase;

an OHED hydratase;

an OHED decarboxylase;

a 6-OHE reductase;

or an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating);

(iii) an HODH aldolase;

an OHED hydratase;

an OHED aminotransferase or an OHED oxidoreductase (aminating);

a 2-AHE reductase;

or a 2-AHD decarboxylase;

(iv) an HODH aldolase;

an OHED hydratase;

an OHED reductase;

a 2-OHD aminotransferase or a 2-OHD oxidoreductase (aminating);

or a 2-AHD decarboxylase;

(v) an HODH aldolase;

an HODH formate-lyase and a pyruvate formate-lyase activating enzyme or an HODH dehydrogenase;

a 3-hydroxyadipyl-CoA dehydratase;

a 2,3-dehydroadipyl-CoA reductase;

an adipyl-CoA dehydrogenase;

or an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating);

(vi) an HODH aldolase;

an OHED hydratase;

an OHED formate-lyase and a pyruvate formate-lyase activating enzyme or OHED dehydrogenase;

a 2,3-dehydroadipyl-CoA reductase;

an adipyl-CoA dehydrogenase;

or an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating); and

(vii) an HODH aldolase;

an OHED hydratase;

an OHED reductase;

a 2-OHD formate-lyase and a pyruvate formate-lyase activating enzyme or a 2-OHD dehydrogenase;

an adipyl-CoA dehydrogenase;

or an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating).

103. The non-naturally occurring microbial organism of claim 95, wherein said microbial organism comprises a set of exogenous nucleic acids encoding 6-ACA pathway enzymes, said set of exogenous nucleic acids encoding:

(i) an HODH aldolase;

an OHED hydratase;

an OHED reductase;

a 2-OHD decarboxylase; and

an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating);

(ii) an HODH aldolase;

an OHED hydratase;

an OHED decarboxylase;

a 6-OHE reductase; and

an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating);

(iii) an HODH aldolase;

an OHED hydratase;

an OHED aminotransferase or an OHED oxidoreductase (aminating);

a 2-AHE reductase; and

a 2-AHD decarboxylase;

(iv) an HODH aldolase;

an OHED hydratase;

an OHED reductase;

a 2-OHD aminotransferase or a 2-OHD oxidoreductase (aminating); and

a 2-AHD decarboxylase;

(v) an HODH aldolase;

an HODH formate-lyase and a pyruvate formate-lyase activating enzyme or an HODH dehydrogenase;

a 3-hydroxyadipyl-CoA dehydratase;

a 2,3-dehydroadipyl-CoA reductase;

an adipyl-CoA dehydrogenase; and

an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating);

(vi) an HODH aldolase;

an OHED hydratase;

an OHED formate-lyase and a pyruvate formate-lyase activating enzyme or OHED dehydrogenase;

a 2,3-dehydroadipyl-CoA reductase;

an adipyl-CoA dehydrogenase; and

an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating);

or

(vii) an HODH aldolase;

an OHED hydratase;

an OHED reductase;

a 2-OHD formate-lyase and a pyruvate formate-lyase activating enzyme or a 2-OHD dehydrogenase;

an adipyl-CoA dehydrogenase; and

an adipate semialdehyde aminotransferase or an adipate semialdehyde oxidoreductase (aminating).

97-102. -102. (canceled)

104-134. -134. (canceled)

135. A non-naturally occurring microbial organism, comprising a microbial organism having a hexamethylenediamine (HMDA) pathway comprising at least one exogenous nucleic acid encoding a HMDA pathway enzyme expressed in a sufficient amount to produce HMDA, said HMDA pathway comprising a glutamyl-CoA transferase, a glutamyl-CoA ligase, a beta-ketothiolase, an 3-oxo-6-aminopimeloyl-CoA oxidoreductase, a 3-hydroxy-6-aminopimeloyl-CoA dehydratase, a 6-amino-7-carboxyhept-2-enoyl-CoA reductase, a 6-aminopimeloyl-CoA reductase (aldehyde forming), a 2-amino-7-oxoheptanoate aminotransferase, a 2-amino-7-oxoheptanoate aminating oxidoreductase, or a homolysine decarboxylase.

143. The non-naturally occurring microbial organism of claim 135, wherein said microbial organism comprises a set of exogenous nucleic acids encoding HMDA pathway enzymes expressed in a sufficient amount to produce HMDA, said set of exogenous nucleic acids encoding a glutamyl-CoA transferase or a glutamyl-CoA ligase;

a beta-ketothiolase;

a 3-oxo-6-aminopimeloyl-CoA oxidoreductase;

a 3-hydroxy-6-aminopimeloyl-CoA dehydratase;

a 6-amino-7-carboxyhept-2-enoyl-CoA reductase;

a 6-aminopimeloyl-CoA reductase (aldehyde forming);

a 2-amino-7-oxoheptanoate aminotransferase or aminating oxidoreductase; and

a homolysine decarboxylase.

283. The non-naturally occurring microbial organism of any one of claims 135, 146 and 179, wherein said HDMA pathway comprises at least two, three or four exogenous nucleic acids.

285. The non-naturally occurring microbial organism of any one of claims 95, 135, 146, 179 and 229, wherein said exogenous nucleic acid is a heterologous nucleic acid.

286. The non-naturally occurring microbial organism of any one of claims 95, 135, 146, 179 and 229, wherein said non-naturally occurring microbial organism is in a substantially anaerobic culture medium.

288. A method for producing hexamethylenediamine (HMDA), comprising culturing a non-naturally occurring microbial organism of any one of claims 135, 146, and 179 under conditions and for a sufficient period of time to produce HMDA, wherein said conditions comprise substantially anaerobic culture conditions.

136-142. -142. (canceled)

144-145. -145. (canceled)

146. A non-naturally occurring microbial organism, comprising a microbial organism having a hexamethylenediamine (HMDA) pathway comprising at least one exogenous nucleic acid encoding a HMDA pathway enzyme expressed in a sufficient amount to produce HMDA, said HMDA pathway comprising a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate reductase, a 3-oxo-1-carboxyheptanal aminotransferase, a 3-oxo-1-carboxyheptanal aminating oxidoreductase, a 3-oxo-7-aminoheptanoate 3-aminotransferase, a 3-oxo-7-aminoheptanoate 3-aminating oxidoreductase, a 3-oxopimelate kinase, a 5-oxopimeloylphosphonate reductase, a 3-oxopimelate CoA transferase, a 3-oxopimelate ligase, a 5-oxopimeloyl-CoA reductase (aldehyde forming), a 3-oxopimelate aminotransferase, a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate CoA transferase, a 3-aminopimelate ligase, a 5-aminopimeloyl-CoA reductase (aldehyde forming), a 3-aminopimelate kinase, a 5-aminopimeloylphosphonate reductase, a 3-aminopimelate reductase, a 3-amino-7-oxoheptanoate 2,3-aminomutase, a 2-amino-7-oxoheptanoate 7-aminotransferase, a 2-amino-7-oxoheptanoate aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, a homolysine decarboxylase, a 3-aminopimelate 2,3-aminomutase, a 2-aminopimelate kinase, a 2-aminopimelate CoA transferase, a 2-aminopimelate CoA ligase, a 2-aminopimelate reductase, a 6-aminopimeloylphosphonate reductase, a 6-aminopimeloyl-CoA reductase (aldehyde forming), a 3-amino-7-oxoheptanoate 7-aminotransferase or a 3-amino-7-oxoheptanoate aminating oxidoreductase.

147. The non-naturally occurring microbial organism of claim 146, wherein said HMDA pathway comprises a pathway selected from the group consisting of:

(i) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate reductase, a 3-oxo-1-carboxyheptanal 7-aminotransferase, a 3-oxo-1-carboxyheptanal 7-aminating oxidoreductase, a 3-oxo-7-aminoheptanoate 3-aminotransferase, a 3-oxo-7-aminoheptanoate 3-aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(ii) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate kinase, a 5-oxopimeloylphosphonate reductase, a 3-oxo-1-carboxyheptanal 7-aminotransferase, a 3-oxo-1-carboxyheptanal 7-aminating oxidoreductase, a 3-oxo-7-aminoheptanoate 3-aminotransferase, a 3-oxo-7-aminoheptanoate 3-aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(iii) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate CoA transferase, 3-oxopimelate CoA ligase, a 5-oxopimeloyl-CoA reductase (aldehyde forming), a 3-oxo-1-carboxyheptanal 7-aminotransferase, 3-oxo-1-carboxyheptanal 7-aminating oxidoreductase, a 3-oxo-7-aminoheptanoate 3-aminotransferase, a 3-oxo-7-aminoheptanoate 3-aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(iv) comprises a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate reductase, a 3-oxo-1-carboxyheptanal 3-aminotransferase, a 3-oxo-1-carboxyheptanal 3-aminating oxidoreductase, a 3-amino-7-oxoheptanoate 7-aminotransferase, a 3-amino-7-oxoheptanoate 7-aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or homolysine decarboxylase;

(v) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, 3-oxopimeloyl-CoA ligase, a 3-oxopimelate kinase, a 5-oxopimeloylphosphonate reductase, a 3-oxo-1-carboxyheptanal 3-aminotransferase, a 3-oxo-1-carboxyheptanal 3-aminating oxidoreductase, a 3-amino-7-oxoheptanoate 7-aminotransferase, a 3-amino-7-oxoheptanoate 7-aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(vi) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate CoA transferase or a 3-oxopimelate CoA ligase, a 5-oxopimeloyl-CoA reductase (aldehyde forming), a 3-oxo-1-carboxyheptanal 3-aminotransferase, a 3-oxo-1-carboxyheptanal 3-aminating oxidoreductase, a 3-amino-7-oxoheptanoate 7-aminotransferase, 3-amino-7-oxoheptanoate 7-aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(vii) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate reductase, a 3-amino-7-oxoheptanoate 2,3-aminomutase, a 2-amino-7-oxoheptanoate 7-aminotransferase, a 2-amino-7-oxoheptanoate aminating oxidoreductase, or a homolysine decarboxylase;

(viii) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate kinase, a 5-aminopimeloylphosphonate reductase, a 3-amino-7-oxoheptanoate 2,3-aminomutase, a 2-amino-7-oxoheptanoate 7-aminotransferase, a 2-amino-7-oxoheptanoate aminating oxidoreductase, or a homolysine decarboxylase;

(ix) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate CoA transferase, a 3-aminopimelate CoA ligase, a 5-aminopimeloyl-CoA reductase (aldehyde forming), a 3-amino-7-oxoheptanoate 2,3-aminomutase, a 2-amino-7-oxoheptanoate 7-aminotransferase, 2-amino-7-oxoheptanoate aminating oxidoreductase, or a homolysine decarboxylase;

(x) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate reductase, a 3-amino-7-oxoheptanoate 7-aminotransferase, 3-amino-7-oxoheptanoate 7-aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(xi) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate CoA transferase, a 3-aminopimelate CoA ligase, a 5-aminopimeloyl-CoA reductase (aldehyde forming), a 3-amino-7-oxoheptanoate 7-aminotransferase, 3-amino-7-oxoheptanoate aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(xii) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate kinase, a 5-aminopimeloylphosphonate reductase, a 3-amino-7-oxoheptanoate 7-aminotransferase, a 3-amino-7-oxoheptanoate aminating oxidoreductase, a 3,7-diaminoheptanoate 2,3-aminomutase, or a homolysine decarboxylase;

(xiii) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate 2,3-aminomutase, a 2-aminopimelate reductase, a 2-amino-7-oxoheptanoate 7-aminotransferase, a 2-amino-7-oxoheptanoate aminating oxidoreductase, or a homolysine decarboxylase;

(xiv) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate 2,3-aminomutase, a 2-aminopimelate kinase, a 6-aminopimeloylphosphonate reductase, a 2-amino-7-oxoheptanoate 7-aminotransferase, a 2-amino-7-oxoheptanoate aminating oxidoreductase, or a homolysine decarboxylase; and

(xv) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, a 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate 2,3-aminomutase, a 2-aminopimelate CoA transferase, 2-aminopimelate CoA ligase, a 6-aminopimeloyl-CoA reductase (aldehyde forming), a 2-amino-7-oxoheptanoate 7-aminotransferase, 2-amino-7-oxoheptanoate aminating oxidoreductase, or a homolysine decarboxylase.

162. The non-naturally occurring microbial organism of claim 146, wherein said microbial organism comprises a set of exogenous nucleic acids encoding HMDA pathway enzymes, said set of exogenous nucleic acids encoding:

(i) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate reductase;

a 3-oxo-1-carboxyheptanal 7-aminotransferase or a 3-oxo-1-carboxyheptanal 7-aminating oxidoreductase;

a 3-oxo-7-aminoheptanoate 3-aminotransferase or a 3-oxo-7-aminoheptanoate 3-aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(ii) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate kinase;

a 5-oxopimeloylphosphonate reductase;

a 3-oxo-1-carboxyheptanal 7-aminotransferase or a 3-oxo-1-carboxyheptanal 7-aminating oxidoreductase;

a 3-oxo-7-aminoheptanoate 3-aminotransferase or a 3-oxo-7-aminoheptanoate 3-aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(iii) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate CoA transferase or 3-oxopimelate CoA ligase;

a 5-oxopimeloyl-CoA reductase (aldehyde forming);

a 3-oxo-1-carboxyheptanal 7-aminotransferase or 3-oxo-1-carboxyheptanal 7-aminating oxidoreductase;

a 3-oxo-7-aminoheptanoate 3-aminotransferase or a 3-oxo-7-aminoheptanoate 3-aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(iv) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate reductase;

a 3-oxo-1-carboxyheptanal 3-aminotransferase or a 3-oxo-1-carboxyheptanal 3-aminating oxidoreductase;

a 3-amino-7-oxoheptanoate 7-aminotransferase or a 3-amino-7-oxoheptanoate 7-aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(v) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate kinase;

a 5-oxopimeloylphosphonate reductase;

a 3-oxo-1-carboxyheptanal 3-aminotransferase or a 3-oxo-1-carboxyheptanal 3-aminating oxidoreductase;

a 3-amino-7-oxoheptanoate 7-aminotransferase or a 3-amino-7-oxoheptanoate 7-aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(vi) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate CoA transferase or a 3-oxopimelate CoA ligase;

a 5-oxopimeloyl-CoA reductase (aldehyde forming);

a 3-oxo-1-carboxyheptanal 3-aminotransferase or a 3-oxo-1-carboxyheptanal 3-aminating oxidoreductase;

a 3-amino-7-oxoheptanoate 7-aminotransferase or 3-amino-7-oxoheptanoate 7-aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(vii) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate reductase;

a 3-amino-7-oxoheptanoate 2,3-aminomutase;

a 2-amino-7-oxoheptanoate 7-aminotransferase or a 2-amino-7-oxoheptanoate aminating oxidoreductase; and

a homolysine decarboxylase;

(viii) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate kinase;

a 5-aminopimeloylphosphonate reductase;

a 3-amino-7-oxoheptanoate 2,3-aminomutase;

a 2-amino-7-oxoheptanoate 7-aminotransferase or a 2-amino-7-oxoheptanoate aminating oxidoreductase; and

a homolysine decarboxylase;

(ix) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate CoA transferase or a 3-aminopimelate CoA ligase;

a 5-aminopimeloyl-CoA reductase (aldehyde forming);

a 3-amino-7-oxoheptanoate 2,3-aminomutase;

a 2-amino-7-oxoheptanoate 7-aminotransferase or 2-amino-7-oxoheptanoate aminating oxidoreductase; and

a homolysine decarboxylase;

(x) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate reductase;

a 3-amino-7-oxoheptanoate 7-aminotransferase or 3-amino-7-oxoheptanoate 7-aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(xi) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate CoA transferase or a 3-aminopimelate CoA ligase;

a 5-aminopimeloyl-CoA reductase (aldehyde forming);

a 3-amino-7-oxoheptanoate 7-aminotransferase or 3-amino-7-oxoheptanoate aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(xii) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate kinase;

a 5-aminopimeloylphosphonate reductase;

a 3-amino-7-oxoheptanoate 7-aminotransferase or a 3-amino-7-oxoheptanoate aminating oxidoreductase;

a 3,7-diaminoheptanoate 2,3-aminomutase; and

a homolysine decarboxylase;

(xiii) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate 2,3-aminomutase;

a 2-aminopimelate reductase;

a 2-amino-7-oxoheptanoate 7-aminotransferase or a 2-amino-7-oxoheptanoate aminating oxidoreductase; and

a homolysine decarboxylase;

(xiv) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate 2,3-aminomutase;

a 2-aminopimelate kinase;

a 6-aminopimeloylphosphonate reductase;

a 2-amino-7-oxoheptanoate 7-aminotransferase or a 2-amino-7-oxoheptanoate aminating oxidoreductase; and

a homolysine decarboxylase;

or

(xv) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or a 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate 2,3-aminomutase;

a 2-aminopimelate CoA transferase or 2-aminopimelate CoA ligase;

a 6-aminopimeloyl-CoA reductase (aldehyde forming);

a 2-amino-7-oxoheptanoate 7-aminotransferase or 2-amino-7-oxoheptanoate aminating oxidoreductase; and

a homolysine decarboxylase.

148-161. -161. (canceled)

163-178. -178. (canceled)

179. A non-naturally occurring microbial organism, comprising a microbial organism having a hexamethylenediamine (HMDA) pathway comprising at least one exogenous nucleic acid encoding a HMDA pathway enzyme expressed in a sufficient amount to produce HMDA, said HMDA pathway comprising:

(i) a 2-oxo-4-hydroxy-7-aminoheptanoate aldolase, a 2-oxo-4-hydroxy-7-aminoheptanoate dehydratase, a 2-oxo-7-aminohept-3-enoate reductase, a 2-oxo-7-aminoheptanoate aminotransferase, a 2-oxo-7-aminoheptanoate aminotransferase aminating oxidoreductase, a homolysine decarboxylase, a 2-oxo-7-aminoheptanoate decarboxylase, a 6-aminohexanal aminotransferase or a 6-aminohexanal aminating oxidoreductase;

or

(ii) a 2-amino-7-oxosubarate keto-acid decarboxylase, a 2-amino-7-oxoheptanoate decarboxylase, a 6-aminohexanal aminating oxidoreductase, a 6-aminohexanal aminotransferase, a 2-amino-7-oxoheptanoate aminating oxidoreductase, a 2-amino-7-oxoheptanoate aminotransferase, a homolysine decarboxylase, a 2-amino-7-oxosubarate amino acid decarboxylase, a 2-oxo-7-aminoheptanoate aminating oxidoreductase, a 2-oxo-7-aminoheptanoate aminotransferase, a 2-oxo-7-aminoheptanoate decarboxylase, a 2-amino-7-oxosubarate aminating oxidoreductase, a 2-amino-7-oxosubarate aminotransferase or a 2,7-diaminosubarate decarboxylase.

185. The non-naturally occurring microbial organism of claim 179, wherein said microbial organism comprises a set of exogenous nucleic acids encoding HMDA pathway enzymes expressed in a sufficient amount to produce HMDA, said set of exogenous nucleic acids encoding:

(i) a 2-oxo-4-hydroxy-7-aminoheptanoate aldolase;

a 2-oxo-4-hydroxy-7-aminoheptanoate dehydratase;

a 2-oxo-7-aminohept-3-enoate reductase;

a 2-oxo-7-aminoheptanoate aminotransferase or a 2-oxo-7-aminoheptanoate aminating oxidoreductase; and

a homolysine decarboxylase;

(ii) a 2-oxo-4-hydroxy-7-aminoheptanoate aldolase;

a 2-oxo-4-hydroxy-7-aminoheptanoate dehydratase;

a 2-oxo-7-aminohept-3-enoate reductase;

a 2-oxo-7-aminoheptanoate decarboxylase; and

a 6-aminohexanal aminotransferase or 6-aminohexanal aminating oxidoreductase;

(iii) a 2-amino-7-oxosubarate aminating oxidoreductase or 2-amino-7-oxosubarate aminotransferase;

a 2,7-diaminosubarate decarboxylase; and

a homolysine decarboxylase;

(iv) a 2-amino-7-oxosubarate amino acid decarboxylase;

a 2-oxo-7-aminoheptanoate aminating oxidoreductase or a 2-oxo-7-aminoheptanoate aminotransferase; and

a homolysine decarboxylase;

(v) a 2-amino-7-oxosubarate amino acid decarboxylase;

a 2-oxo-7-aminoheptanoate decarboxylase; and

a 6-aminohexanal aminating oxidoreductase or a 6-aminohexanal aminotransferase;

(vi) a 2-amino-7-oxosubarate keto-acid decarboxylase;

a 2-amino-7-oxoheptanoate decarboxylase; and

a 6-aminohexanal aminating oxidoreductase or a 6-aminohexanal aminotransferase;

or

(vii) a 2-amino-7-oxosubarate keto-acid decarboxylase;

a 2-amino-7-oxoheptanoate aminating oxidoreductase or a 2-amino-7-oxoheptanoate aminotransferase; and

a homolysine decarboxylase.

206. The non-naturally occurring microbial organism of claim 179, part (ii), further comprising a 2-amino-7-oxosubarate pathway comprising at least one exogenous nucleic acid encoding a 2-amino-7-oxosubarate pathway enzyme expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said 2-amino-7-oxosubarate pathway comprising a 2-amino-5-hydroxy-7-oxosubarate aldolase, a 2-amino-5-hydroxy-7-oxosubarate dehydratase, or a 2-amino-5-ene-7-oxosubarate reductase.

210. The non-naturally occurring microbial organism of claim 185, part (iii) further comprising a 2-amino-7-oxosubarate pathway comprising a second set of exogenous nucleic acids encoding 2-amino-7-oxosubarate pathway enzymes expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said second set of exogenous nucleic acids encoding a 2-amino-5-hydroxy-7-oxosubarate aldolase;

a 2-amino-5-hydroxy-7-oxosubarate dehydratase; and

a 2-amino-5-ene-7-oxosubarate reductase.

214. The non-naturally occurring microbial organism of claim 185, part (iv), further comprising a 2-amino-7-oxosubarate pathway comprising a second set of exogenous nucleic acids encoding 2-amino-7-oxosubarate pathway enzymes expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said second set of exogenous nucleic acids encoding a 2-amino-5-hydroxy-7-oxosubarate aldolase;

a 2-amino-5-hydroxy-7-oxosubarate dehydratase; and

a 2-amino-5-ene-7-oxosubarate reductase.

218. The non-naturally occurring microbial organism of claim 185, part (v), further comprising a 2-amino-7-oxosubarate pathway comprising a second set of exogenous nucleic acids encoding 2-amino-7-oxosubarate pathway enzymes expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said second set of exogenous nucleic acids encoding a 2-amino-5-hydroxy-7-oxosubarate aldolase;

a 2-amino-5-hydroxy-7-oxosubarate dehydratase; and

a 2-amino-5-ene-7-oxosubarate reductase.

222. The non-naturally occurring microbial organism of claim 185, part (vi), further comprising a 2-amino-7-oxosubarate pathway comprising a second set of exogenous nucleic acids encoding 2-amino-7-oxosubarate pathway enzymes expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said second set of exogenous nucleic acids encoding a 2-amino-5-hydroxy-7-oxosubarate aldolase;

a 2-amino-5-hydroxy-7-oxosubarate dehydratase; and

a 2-amino-5-ene-7-oxosubarate reductase.

226. The non-naturally occurring microbial organism of claim 185, part (vii), further comprising a 2-amino-7-oxosubarate pathway comprising a second set of exogenous nucleic acids encoding 2-amino-7-oxosubarate pathway enzymes expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said second set of exogenous nucleic acids encoding a 2-amino-5-hydroxy-7-oxosubarate aldolase;

a 2-amino-5-hydroxy-7-oxosubarate dehydratase; and

a 2-amino-5-ene-7-oxosubarate reductase.

180-184. -184. (canceled)

186-205. -205. (canceled)

207-209. -209. (canceled)

211-213. -213. (canceled)

215-217. -217. (canceled)

219-221. -221. (canceled)

223-225. -225. (canceled)

227-228. -228. (canceled)

229. A non-naturally occurring microbial organism, comprising a microbial organism having a 6-aminocaproic acid (6-ACA) pathway comprising at least one exogenous nucleic acid encoding a 6-ACA pathway enzyme expressed in a sufficient amount to produce 6-ACA, said 6-ACA pathway comprising a pathway selected from the group consisting of:

(i) a glutamyl-CoA transferase, a glutamyl-CoA ligase, a beta-ketothiolase, an 3-oxo-6-aminopimeloyl-CoA oxidoreductase, a 3-hydroxy-6-aminopimeloyl-CoA dehydratase, a 6-amino-7-carboxyhept-2-enoyl-CoA reductase, a 6-aminopimeloyl-CoA reductase (aldehyde forming), or a 2-aminopimelate decarboxylase;

(ii) a glutaryl-CoA beta-ketothiolase, a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase, a 3-oxopimeloyl-CoA ligase, a 3-oxopimelate aminotransferase, 3-oxopimelate aminating oxidoreductase, a 3-aminopimelate 2,3-aminomutase, or a 2-aminopimelate decarboxylase;

(iii) a homolysine 2-monooxygenase; and

(iv) a 2-amino-7-oxosubarate keto-acid decarboxylase, a 2-amino-7-oxoheptanoate decarboxylase, a 2-amino-7-oxoheptanoate oxidoreductase, a 2-aminopimelate decarboxylase, a 6-aminohexanal oxidoreductase, a 2-amino-7-oxoheptanoate decarboxylase, or a 2-amino-7-oxosubarate amino acid decarboxylase.

235. The non-naturally occurring microbial organism of claim 229, wherein said microbial organism comprises a set of exogenous nucleic acids encoding 6-ACA pathway enzymes expressed in a sufficient amount to produce 6-ACA, said set of exogenous nucleic acids encoding:

(i) a glutamyl-CoA transferase or a glutamyl-CoA ligase;

a beta-ketothiolase;

a 3-oxo-6-aminopimeloyl-CoA oxidoreductase;

a 3-hydroxy-6-aminopimeloyl-CoA dehydratase;

a 6-amino-7-carboxyhept-2-enoyl-CoA reductase;

a 6-aminopimeloyl-CoA reductase (aldehyde forming); and

a 2-aminopimelate decarboxylase;

(ii) a glutaryl-CoA beta-ketothiolase;

a 3-oxopimeloyl-CoA hydrolase, a 3-oxopimeloyl-CoA transferase or a 3-oxopimeloyl-CoA ligase;

a 3-oxopimelate aminotransferase or 3-oxopimelate aminating oxidoreductase;

a 3-aminopimelate 2,3-aminomutase; and

a 2-aminopimelate decarboxylase;

(iii) a 2-amino-7-oxosubarate keto-acid decarboxylase;

a 2-amino-7-oxoheptanoate oxidoreductase; and

a 2-aminopimelate decarboxylase;

(iv) a 2-amino-7-oxosubarate keto-acid decarboxylase;

a 2-amino-7-oxoheptanoate decarboxylase; and

a 6-aminohexanal oxidoreductase;

or

(v) a 2-amino-7-oxosubarate amino acid decarboxylase;

a 2-amino-7-oxoheptanoate decarboxylase; and

a 6-aminohexanal oxidoreductase.

258. The non-naturally occurring microbial organism of claim 229, part (iv), further comprising a 2-amino-7-oxosubarate pathway comprising at least one exogenous nucleic acid encoding a 2-amino-7-oxosubarate pathway enzyme expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said 2-amino-7-oxosubarate pathway comprising a 2-amino-5-hydroxy-7-oxosubarate aldolase, a 2-amino-5-hydroxy-7-oxosubarate dehydratase, or a 2-amino-5-ene-7-oxosubarate reductase.

268. The non-naturally occurring microbial organism of claim 235, part (v), further comprising a 2-amino-7-oxosubarate pathway comprising a second set of exogenous nucleic acids encoding 2-amino-7-oxosubarate pathway enzymes expressed in a sufficient amount to produce 2-amino-7-oxosubarate, said second set of exogenous nucleic acids encoding a 2-amino-5-hydroxy-7-oxosubarate aldolase;

a 2-amino-5-hydroxy-7-oxosubarate dehydratase; and

a 2-amino-5-ene-7-oxosubarate reductase.

284. The non-naturally occurring microbial organism of claim 95 or 229, wherein said 6-ACA pathway comprises at least two, three or four exogenous nucleic acids.

287. A method for producing 6-aminocaproic acid (6-ACA), comprising culturing a non-naturally occurring microbial organism of claim 95 or 229 under conditions and for a sufficient period of time to produce 6-ACA, wherein said conditions comprise substantially anaerobic culture conditions.

230-234. -234. (canceled)

236-257. -257. (canceled)

259-267. -267. (canceled)

269-282. -282. (canceled)