Methods of producing 7-carbon chemicals via c1 carbon chain elongation associated with coenzyme b synthesis

Abstract

This document describes biochemical pathways for producing pimelic acid, 7-aminoheptanoic acid, 7-hydroxyheptanoic acid, heptamethylenediamine or 1,7-heptanediol by forming one or two terminal functional groups, each comprised of carboxyl, amine or hydroxyl group, in a C7 aliphatic backbone substrate. These pathways, metabolic engineering and cultivation strategies described herein rely on the C1 elongation enzymes or homolog associated with coenzyme B biosynthesis.

1 .- 32 . (canceled) 
     
     
         33 . A recombinant host comprising at least one exogenous nucleic acid encoding (i) a (homo) n citrate synthase classified under EC 2.3.3.14 or EC 2.3.3.13, (ii) a (homo) n citrate dehydratase and a (homo) n aconitate hydratase classified under EC 4.2.1.114, EC 4.2.1.36, or EC 4.2.1.33, (iii) an iso(homo) n citrate dehydrogenase classified under EC 1.1.1.85, EC 1.1.1.87, or EC 1.1.1.286, and/or (iv) an indolepyruvate decarboxylase classified under EC 4.1.1.43 or EC 4.1.1.74, or a 2-oxoglutarate dehydrogenase complex comprising one or more enzymes classified under EC 1.2.4.2, EC 1.8.1.4, and EC 2.3.1.61, said host producing pimeloyl-CoA or pimelate semialdehyde. 
     
     
         34 . The recombinant host of  claim 33 , further comprising at least one exogenous nucleic acid encoding one or more of a thioesterase classified under EC 3.1.2.-, an aldehyde dehydrogenase classified under EC 1.2.1.3, a 7-oxoheptanoate dehydrogenase classified under EC 1.2.1.-, a 6-oxohexanoate dehydrogenase classified under EC 1.2.1.-, a glutaconate CoA-transferase classified under EC 2.8.3.12, a reversible succinyl-CoA-ligase classified under EC 6.2.1.5, an acetylating aldehyde dehydrogenase classified under EC 1.2.1.10, or a carboxylate reductase classified under EC 1.2.99.6, said host producing pimelic acid or pimelate semialdehyde. 
     
     
         35 . The recombinant host of  claim 34 , further comprising at least one exogenous nucleic acid encoding a ω-transaminase classified under EC 2.6.1.-, said host producing 7-aminoheptanoate. 
     
     
         36 . The recombinant host of  claim 34 , further comprising one or more of a 4-hydroxybutyrate dehydrogenase classified under EC 1.1.1.-, a 5-hydroxypentanoate dehydrogenase classified under EC 1.1.1.-, or a 6-hydroxyhexanoate dehydrogenase classified under EC 1.1.1.258, said host producing 7-hydroxyheptanoic acid. 
     
     
         37 . The recombinant host of  claim 33 , further comprising at least one exogenous nucleic acid encoding a ω-transaminase classified under EC 2.6.1.-, a deacetylase classified under EC 3.5.1.62, a N-acetyl transferase classified under EC 2.3.1.32 or an alcohol dehydrogenase classified under EC 1.1.1.-, said host producing heptamethylenediamine. 
     
     
         38 . The recombinant host of  claim 36 , further comprising at least one exogenous nucleic acid encoding a (i) carboxylate reductase classified under EC 1.2.99.6 enhanced by a phosphopantetheinyl transferase classified under EC 2.7.8.- or (ii) an alcohol dehydrogenase classified under EC 1.1.1.-, said host producing 1,7-heptanediol.